Learn more about key efficacy endpoints as oncology professionals review the data reported in IMbrave150.
[00:00:00]
CHERYL TIMA: Hi, my name is Cheryl Tima and I am a Senior Thought Leader Liaison in the Gastroenterology Branch of Genentech Oncology. I am thrilled to introduce you to the IMbrave150 Ask the Multidisciplinary Team video series. Today's video will feature an esteemed panel discussing key efficacy endpoints from the IMbrave150 trial that may help you and members of your healthcare team to inform treatment decisions in your patients with first line unresectable and/or metastatic HCC. I'm excited to introduce you to our Multidisciplinary Panel, which consists of Dr. Bonilla, Dr. Salgia, and Dr. Salem.
ARTURO LOAIZA-BONILLA: Hi, I'm Dr. Arturo Loaiza-Bonilla. I'm Program Director for Gastrointestinal Oncology, Medical Director of Clinical Research, and Vice Chairman of the Department of Medical Oncology at Cancer Treatment Centers of America.
RIAD SALEM: Hello, I am Dr. Riad Salem, Professor of Radiology, Medicine, and Surgery, Vice Chair for Image Guided Therapy in the Department of Radiology, and Chief of Vascular and Interventional Radiology in the Department of Radiology at the Northwestern Feinberg School of Medicine.
REENA SALGIA: Hello, I am Dr. Reena Salgia, Medical Director of the Liver Cancer Clinic and Program Director for the Gastroenterology and Transplant Hepatology Fellowship Programs at the Henry Ford Health System in Detroit, Michigan.
CHERYL TIMA: Wonderful. Thanks for those introductions. Before we get started, I would like to note the following on behalf of the panel. This program is presented on behalf of Genentech, and the information presented is consistent with FDA guidelines. The panelists in this video have been compensated by Genentech to serve as speakers for this program. This program is intended to provide general information about Tecentriq and Avastin and not medical advice for any particular patient. Any adverse events included in this presentation have already been reported to Genentech Drug Safety, and no action is required by any member of the audience. This program may be monitored by Genentech for adherence to program requirements. And all materials are the property of Genentech and may not be recorded, photographed, copied, or reproduced. Tecentriq and Avastin is the first FDA approved immunotherapy combination for first line unresectable and/or metastatic HCC in patients who have not received prior systemic therapy. As you can see here, there are several warnings and precautions for this combination therapy. We will be discussing the safety information throughout the program. However, please note that the full warnings and precautions, as well as all other important safety information, can be found in the full Tecentriq prescribing information. As you may already be aware, IMbrave150 was the first successful Phase 3 study of cancer immunotherapy combination versus sorafenib in first line unresectable and/or metastatic HCC. The IMbrave150 trial investigated Tecentriq plus Avastin versus sorafenib in 501 patients with previously untreated locally advanced unresectable and/or metastatic HCC until disease progression or unacceptable toxicity. One of the co-primary endpoints of the IMbrave150 trial was overall survival. When we look at the Kaplan-Meier curve, we see that the median overall survival, or OS, was not reached at the time of the clinical data cutoff for the primary analysis. What does this mean? And how might an HCP explain this to a more junior colleague or a team member who might need some additional clarification?
ARTURO LOAIZA-BONILLA: Thank you so much for that introduction earlier. On the information of the data, so that's a very relevant question. So discussions on overall survival often come up in conversations between us, healthcare providers in our team -- our team discussions, and also with fellows and residents who are trainees that we rotate with them in clinic. And when evaluating the efficacy of a therapy, this is a very relevant point. Tecentriq and Avastin demonstrated an unprecedent statistically significant overall survival benefit. The combination resulted in a 42 percent reduced risk of death compared with sorafenib. When educating my team on the overall survival results from the IMbrave150, I will often refer to what we call the Kaplan-Meier overall survival curves. As you can see here, with the Kaplan-Meier overall survival curves, at the time of the clinical data cutoff, which was August 2019, the median overall survival in the Tecentriq plus Avastin arm was what we call not reached, compared with 13.2 months in the sorafenib arm. These results of not reached means that more than 50 percent of the patients within in the Tecentriq plus Avastin arm were still alive at the time of the analysis.
RIAD SALEM: I think it will be very important for healthcare teams to continue to monitor and discuss updates to this kind of data Dr. Bonilla is discussing. In the case of the IMbrave150 trial, there was a one-year follow-up on overall survival.
[00:05:00]
In a descriptive follow-up overall survival analysis conducted on August 31, 2020, the IMbrave150 trial resulted in a median overall survival of 19.2 months for Tecentriq plus Avastin versus 13.4 months with sorafenib with a hazard ratio of 0.66. Please note, however, this is a descriptive analysis only, so the p value cannot formally be claimed.
REENA SALGIA: The other co-primary endpoint that was included from the IMbrave150 was progression free survival, or PFS, as determined by independent review facility per a response evaluation criteria in solid tumors, version 1.1, or RECIST criteria 1.1. In IMbrave150, Tecentriq and Avastin significantly improved the median PFS, demonstrating a 41 percent reduction in disease progression or death compared with sorafenib. The median PFS was 6.8 months with Tecentriq and Avastin versus 4.3 months with placebo.
CHERYL TIMA: Great. Thank you for that perspective. In addition to the OS and PFS, which we just discussed, what other clinically meaningful endpoints or data from the IMbrave150 trial might a healthcare team discuss?
RIAD SALEM: Many healthcare providers have also taken notice of the overall response rate, or ORR, as well as complete and partial responses reported in the IMbrave150 trial. Overall response rate was a secondary endpoint of the IMbrave150 trial that was evaluated by both mRECIST and RECIST version 1.1. Based on the RECIST version 1.1 criteria, the bar graph shown here illustrates that Tecentriq and Avastin demonstrated more than double the objective response rate versus sorafenib. Complete responses were observed in 7 percent of responders treated with Tecentriq and Avastin versus 0 percent of those treated with sorafenib. Partial responses were observed in 21 percent of responders treated with Tecentriq plus Avastin versus 12 percent of those treated with sorafenib. Overall response rate was also assessed by the modified RECIST criteria, in which Tecentriq plus Avastin demonstrated almost triple the overall response rate versus sorafenib, as shown on this slide.
ARTURO LOAIZA-BONILLA: Thank you for that. In addition to the efficacy, my colleagues and I also consider what we call the safety profile of a treatment before putting any patients on a therapy. So, in the IMbrave150 study, Tecentriq plus Avastin demonstrated what we call an established safety profile. On the slide here you can see what we mention as a tornado plot of select adverse reactions that occur at a frequency of at least 10 percent in patients in either arm of treatment with Tecentriq and Avastin or sorafenib, and at least a 5 percent difference between arms. The overall incidence of treatment-related Grade 3 or 4 adverse reactions was 36 percent with Tecentriq plus Avastin versus 46 percent with sorafenib. Overall, Tecentriq plus Avastin has an established safety profile, which is consistent with the previously known safety profiles of the individual medicines. Here, we have the full adverse reaction table, showing all the reactions that occurred at a frequency of greater than or equal to 10 percent in patients receiving Tecentriq plus Avastin.
CHERYL TIMA: Great. Thank you. I want to thank you for that answer and the panel for joining us today for this insightful discussion on the importance of educating fellow team members on key clinical endpoints from the IMbrave150 trial. A deeper understanding of the IMbrave150 data may help you and your team inform treatment decisions for your patients with first line unresectable and/or metastatic HCC. We hope that you've found this chapter of the IMbrave150 Ask the Multidisciplinary Team video series to be enlightening and informative for your practice. To hear more from our multidisciplinary panel on the IMbrave150 study, be sure to view additional episodes of the Ask the Multidisciplinary Team series on tecentriq.com. Now, please continue watching to hear about the important safety information.
SPEAKER 1: For serious adverse reactions, please refer to the full prescribing information for important dose management information specific to adverse reactions. Tecentriq is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 or the PD-ligand 1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, they can also manifest after discontinuation of treatment.
[00:10:00]
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue Tecentriq depending on severity. In general, if Tecentriq requires interruption or discontinuation, administer systemic corticosteroid therapy until improvement to Grade 1 or less, then initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. The following immune-mediated adverse reactions may not include all possible severe and fatal immune-mediated reactions. Tecentriq can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune mediated pneumonitis occurred in 3 percent of patients receiving Tecentriq as a single agent, including fatal, Grade 4, Grade 3, and Grade 2 adverse reactions. Pneumonitis led to permanent discontinuation of Tecentriq in 0.5 percent and withholding of Tecentriq in 1.5 percent of patients. Systemic corticosteroids were required in 55 percent of patients with pneumonitis. Tecentriq can cause immune-mediated colitis. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal bleeding. Cytomegalovirus infection reactivation has been reported in patients with corticosteroid refractory immune-mediated colitis. In cases of corticosteroid refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Colitis led to permanent discontinuation of Tecentriq in 0.2 percent and withholding of Tecentriq in 0.5 percent of patients. System corticosteroids were required in 50 percent of patients with colitis. Colitis resolved in 73 percent of the 26 patients. Of the 12 patients in whom Tecentriq was withheld for colitis, eight reinitiated treatment with Tecentriq after symptom improvement. Of these, 25 percent had recurrence of colitis. Tecentriq can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.8 percent of patients receiving Tecentriq as a single agent, including fatal, Grade 4, Grade 3, and Grade 2 adverse reactions. Hepatitis led to permanent discontinuation of Tecentriq in 0.2 percent and withholding of Tecentriq in 0.2 percent of patients. Systemic corticosteroids were required in 25 percent of patients with hepatitis. Hepatitis resolved in 50 percent of the 48 patients. Of the six patients in whom Tecentriq was withheld for hepatitis, four reinitiated treatment with Tecentriq after symptom improvement. Of these, none had recurrence of hepatitis. Tecentriq can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Adrenal insufficiency occurred in 0.4 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Adrenal insufficiency led to permanent discontinuation of Tecentriq in one patient and withhold of Tecentriq in one patient. Systemic corticosteroids were required in 81 percent of patients with adrenal insufficiency. Of these, three patients remained on systemic corticosteroids. The single patient in whom Tecentriq was withheld for adrenal insufficiency did not reinitiate Tecentriq. Tecentriq can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect, such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Hypophysitis occurred in less than 0.1 percent of patients receiving Tecentriq as a single agent, including Grade 2 adverse reactions. Hypophysitis led to permanent discontinuation of Tecentriq in one patient and no patients required withholding of Tecentriq. Systemic corticosteroids were required in 50 percent of patients with hypophysitis. Hypophysitis did not resolve in these two patients. Tecentriq can cause immune-mediated thyroid disorders.
[00:15:00]
Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or medical management for hyperthyroidism as clinically indicated. Thyroiditis occurred in 0.2 percent of patients receiving Tecentriq as a single agent, including Grade 2 adverse reactions. Thyroiditis did not lead to permanent discontinuation of Tecentriq in any of these patients but led to withholding of Tecentriq in one patient. Hormone replacement therapy was required in 75 percent of patients with thyroiditis. Systemic corticosteroids were required in 25 percent of patients with thyroiditis. Thyroiditis resolved in 50 percent of patients. The single patient in whom Tecentriq was withheld for thyroiditis reinitiated Tecentriq. This patient did not have recurrence of thyroiditis. Hyperthyroidism occurred in 0.8 percent of patient receiving Tecentriq as a single agent, including Grade 2 adverse reactions. Hyperthyroidism did not lead to permanent discontinuation of Tecentriq in any of these patients but led to withholding of Tecentriq in 0.1 percent of patients. Antithyroid therapy was required in 29 percent of patients with hyperthyroidism. Of these six patients, the majority remained on antithyroid treatment. Of the three patients in whom Tecentriq was withheld for hyperthyroidism, one patient reinitiated Tecentriq. This patient did not have recurrence of hyperthyroidism. Hypothyroidism occurred in 4.9 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Hypothyroidism did not lead to permanent discontinuation of Tecentriq in any of these patients but led to withholding of Tecentriq in 0.6 percent of patients. Hormone replacement therapy was required in 81 percent of patients with hypothyroidism. The majority of patients with hypothyroidism remained on thyroid hormone replacement. Of the 17 patients in whom Tecentriq was withheld for hypothyroidism, eight reinitiated Tecentriq after symptom improvement. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin, as clinically indicated. Type 1 diabetes mellitus occurred in 0.3 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Type 1 diabetes mellitus led to permanent discontinuation of Tecentriq in one patient and withholding of Tecentriq in two patients. Treatment with insulin was required for all patients with confirmed Type 1 diabetes mellitus and insulin therapy was continued long-term. Of the two patients in whom Tecentriq was withheld for Type 1 diabetes mellitus, both reinitiated Tecentriq treatment. Tecentriq can cause immune-mediated nephritis. Immune-mediated nephritis with renal disfunction occurred in less than 0.1 percent of patients receiving Tecentriq as a single agent and this adverse reaction was a Grade 3 adverse reaction. Nephritis led to permanent discontinuation of Tecentriq in this patient. This patient required systemic corticosteroids. In this patient, nephritis did not resolve. Tecentriq can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, DRESS, and toxic epidermal necrolysis has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated dermatologic adverse reactions occurred in 0.6 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of Tecentriq in 0.1 percent and withholding of Tecentriq in 0.2 percent of patients. System corticosteroids were required in 20 percent of patients with dermatologic adverse reactions. Dermatologic adverse reactions resolved in 87 percent of the 15 patients. Of the four patients in whom Tecentriq was withheld for immune-mediated dermatologic adverse reactions, none reinitiated Tecentriq. The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1 percent in patients who received Tecentriq or were reported with the use of other PD-1/PD-L1 blocking antibodies. Cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur
[00:20:00]
If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis, sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection. Tecentriq can cause severe or life-threatening infusion related reactions. Monitor for signs and symptoms of infusion related reactions. Interrupt, slow the rate of, or permanently discontinue Tecentriq based on the severity. For Grade 1 or 2 infusion related reactions, consider using pre-medications with subsequent doses. Infusion related reactions occurred in 1.3 percent of patients receiving Tecentriq as a single agent, including Grade 3 reactions. The frequency and severity of infusion related reactions were similar across the recommended dose range. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant related complications include hyperacute graft-versus-host disease, acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity condition, and steroid-requiring febrile syndrome. These complications may occur despite intervening therapy between PD-1/PD-L1 blockage and allogenic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogenic HSCT. Based on its mechanism of action, Tecentriq can cause fetal harm when administered to a pregnant woman. There are no available data on the use of Tecentriq in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus, resulting in fetal death. Verify pregnancy status of females of reproductive potential prior to initiating Tecentriq. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with Tecentriq and for at least five months after the last dose. There is no information regarding the presence of Tecentriq in human milk, the effects on the breastfed infant, or the effects on milk production. As human IGG is excreted in human milk, the potential for absorption and harm to the infant is unknown. Because of the potential for serious adverse reactions in breastfed infants from Tecentriq, advise female patients not to breastfeed while taking Tecentriq, and for at least five months after the last dose. Based on animal studies, Tecentriq may impair fertility in females of reproductive potential while receiving treatment. The most common adverse reactions in patients who receive Tecentriq in combination with bevacizumab for HCC were hypertension, fatigue/asthenia, and proteinuria. You may report side effects to the FDA at 1-800-FDA-1088, or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555. Please see the full prescribing information for additional important safety information.
View perspectives from oncology professionals as they discuss the value of multidisciplinary care when treating patients.
[00:00:00]
DAVID ALLRED: Hi, my name is David Allred. I'm a Senior Thought Leader Liaison in the Gastroenterology Branch of Genentech Oncology. I am thrilled to introduce you to the Genentech Ask the Multidisciplinary Team video series. Today's video will feature an esteemed panel discussing the value of the multidisciplinary team to inform treatment decisions for patients with unresectable and/or metastatic HCC. Before we get started, I would like to note the following on behalf of the panel. This program is presented on behalf of Genentech, and the information presented is consistent with FDA guidelines. The panelists in this video have been compensated by Genentech to serve as speakers for this program. This program is intended to provide general information about hepatocellular carcinoma and not medical advice for any particular patient. This program may be monitored by Genentech for adherence to program requirements. All materials are the property of Genentech and may not be recorded, photographed, copied, or reproduced. I'm excited to introduce you our Multidisciplinary Panel, which consists of Dr. Bonilla, medical oncologist, Dr. Salgia, hepatologist, and Dr. Salem, interventional radiologist.
ARTURO LOAIZA-BONILLA: Hi, I'm Dr. Arturo Loaiza-Bonilla, Program Director for Gastrointestinal Oncology, Medical Director of Clinical Research, and Vice Chairman of the Department of Medical Oncology at Cancer Treatment Centers of America.
RIAD SALEM: Hello, I am Dr. Riad Salem, Professor of Radiology, Medicine, and Surgery, Vice Chair for Image Guided Therapy in the Department of Radiology, and Chief of Vascular and Interventional Radiology in the Department of Radiology at the Northwestern Feinberg School of Medicine.
REENA SALGIA: Hello, I am Dr. Reena Salgia, Medical Director of the Liver Cancer Clinic and Program Director of the Gastroenterology and Transplant Hepatology Fellowships at the Henry Ford Health System in Detroit, Michigan.
DAVID ALLRED: Thank you. With the evolving treatment landscape for HCC, there's a growing need for expertise across different multidisciplinary team, or MDT, disciplines. Could you please describe the value of the MDT in the treatment of patients with HCC
REENA SALGIA: Thank you for that question. Each of the different disciplines in a multidisciplinary team comes with its own unique perspectives and treatment for HCC based on existing treatment algorithms and the available evidence.
RIAD SALEM: The treatment landscape in HCC is rapidly evolving to include multimodal approaches (example, combination of locoregional therapy with systemic, adjuvant therapy after locoregional therapy, et cetera). Studies have demonstrated the impact of the MDT in HCC management and survival. Early MDT involvement may help guide appropriate therapies for patients and will impact patient outcomes, including improving survival. Although an MDT's considered an essential part of successful HCC treatment, fewer than half of patients with HCC in the United States receive multidisciplinary care.
ARTURO LOAIZA-BONILLA: Thank you for that. I think it's a very important point. So MDT discussions will be important in implementing evidence-based practice decisions, in assessing new therapies for HCC across multiple disciplines. Hepatologists and medical oncologists, for example, can provide access to clinical trials, additive care, and survivorship support. It can also provide oversight of care in the management of hypertension, variceal surveillance, and hospitalizations that can occur during prolonged therapies. Interventional radiologists can provide input on efficacy, safety, and visibility, or locoregional therapies in treating hepatic lesions. They also provide input in determining the ideal timing of sequential therapies of other treatment options needed in controlling the disease.
DAVID ALLRED: Thank you, Dr. Bonilla. What are your thoughts on AASLD's recommendations that patients be seen or referred to a multidisciplinary team clinic?
REENA SALGIA: According to the AASLD Guidelines, multidisciplinary discussions are recommended to individualize the workup for the management of these patients. Institutions are encouraged to develop their own approach through multidisciplinary discussion and consensus.
RIAD SALEM: It is important to highlight the benefit of multidisciplinary team for all liver lesions, but particularly for LIRADS 4 and LIRADS-m lesions measuring 1 centimeter or more in diameter to develop patient-tailored approaches.
ARTURO LOAZA-BONILLA: Indeed, the management of HCC encompasses multiple disciplines that includes hepatologists, diagnostic radiologists, pathologists, trusted surgeons, surgical oncologists, interventional radiologists, medical oncologists like myself, radiation oncologists, nurses, and palliative care professionals. So it's a very comprehensive, as we mentioned, multidisciplinary team. A recent study showed that the development of a true multidisciplinary clinic with a dedicated tumor board review for HCC patients increased survival.
[00:05:00]
Therefore, HCC patients should be seen in these clinics whenever it's feasible, and if not, are referred to a center with a true multidisciplinary clinic should be considered.
DAVID ALLRED: Thank you for that. I'd like to thank the entire panel for joining us today for this enlightening discussion on the importance of multidisciplinary team approaches when treatment patients with unresectable and/or metastatic HCC. We hope that you found this topic of this chapter of the Ask the Multidisciplinary Team video series both enlightening and informative for your practice.
Join oncology professionals for a multidisciplinary roundtable discussion of a patient case study.
[00:00:00]
ARTURO LOAIZA-BONILLA: Welcome to the Ask the Multidisciplinary Team series for the IMbrave150 trial. I am Dr. Arturo Loaiza-Bonilla, Program Director of Gastrointestinal Oncology, Medical Director of Clinical Research, and Vice Chairman of the Department of Medical Oncology at the Cancer Treatment Centers of America. Today, I am joined by my colleagues, Dr. Riad Salem and Dr. Reena Salgia, to discuss a BCLC HCC patient case study in first line unresectable HCC who may not be eligible for surgery or local regional therapy. This video will highlight how these patients may be eligible for Tecentriq and Avastin, which is the first cancer immunotherapy combination that has been FDA approved to treat first line unresectable and/or metastatic HCC.
RIAD SALEM: Hello, I am Dr. Riad Salem, Professor of Radiology, Medicine, and Surgery, Vice Chair for Image Guided Therapy in the Department of Radiology, and Chief of Vascular and Interventional Radiology in the Department of Radiology at the Northwestern Feinberg School of Medicine.
REENA SALGIA: Hello, I am Dr. Reena Salgia, Medical Director of the Liver Cancer Clinic and Program Director of the Gastroenterology and Transplant Hepatology Fellowships at the Henry Ford Health System in Detroit, Michigan.
ARTURO LOAIZA-BONILLA: Thank you so much for those introductions. Before we get started, I would like to note the following on behalf of the panel. This program is presented on behalf of Genentech, and the information presented is consistent with FDA guidelines. We have been compensated by Genentech to serve as speakers for this program. This program is intended to provide general information about Tecentriq and Avastin and not medical advice for any particular patient. Any adverse events included in this presentation have already been reported to Genentech Drug Safety, and no action is required by any member of the audience. This program may be monitored by Genentech for adherence to program requirements. And all materials are the property of Genentech and may not be recorded, photographed, copied, or reproduced. Tecentriq and Avastin is the first FDA approved immunotherapy combination for first line unresectable and/or metastatic HCC in patients who have not received prior systemic therapy. As you can see here, there are several warnings and precautions for this combination therapy. We will be discussing the safety information throughout the program. However, please note that the full warnings and precautions, as well as all other important safety information, can be found in the full Tecentriq prescribing information. So, to get started, before we dive into today's patient case, I would like to discuss which patients with first line unresectable and/or metastatic HCC will benefit from multidisciplinary discussions like the ones we're having today.
REENA SALGIA: So multidisciplinary assessment may be helpful for patients with unresectable and/or metastatic HCC who have not received prior systemic therapy similar to those that were included in the IMbrave150 study.
RIAD SALEM: The IMbrave150 study included patients with unresectable and/or metastatic disease, including those with adequate liver function, defined as a Child-Pugh class A, Barcelona Clinic Liver Cancer, or BCLC, Stage C HCC, BCLC Stage B HCC, poor prognostic factors, such as extrahepatic spread and macrovascular invasion, and completed treated varices without bleeding.
ARTURO LOAIZA-BONILLA: Thank you for that. Understanding the patient population from the IMbrave150 study is very important as we're discussing today's patient case study. So let's take a closer look now. So, this is Frank, of course, a hypothetical patient. He's a BCLC Stage B patient with unresectable HCC who is further representative from the patients that were involved in the IMbrave150 trial. Based on previous discussions, what stands out for you in Frank's profile?
REENA SALGIA: So, notably, this patient, Frank, would be similar to a patient who would have been included in the IMbrave150 study. So his age is relevant in terms of what kind of therapies we may consider or what type of therapies a patient may be able to tolerate. He is also Child-Pugh A in terms of his liver function, meaning that he continues to have well-compensated or functioning liver, and additionally, his varices were previously treated and eradicated more than six months ago. The patients that were excluded from the IMbrave150 study did have variceal bleeding within six months prior to treatment, untreated, or incompletely treated varices with bleeding or a high risk of bleeding.
ARTURO LOAIZA-BONILLA: Varices is an important factor for the multidisciplinary team, particularly for hepatologists, and we will discuss this topic in more detail later in this video
[00:05:00]
Dr. Salem, as an interventional radiologist, what stood out to you in terms of Frank's profile?
RIAD SALEM: So, if you look at both the NCCN and ASLD guidelines, they recommend diagnostic evaluation for HCC with either multiphase CT or MRI, for patients with cirrhosis, and lesions greater than 10 millimeters on ultrasound or alpha fetoprotein over 20. Based on Frank's profile, Frank has undergone a CT imaging and has two lesions, one in the right lobe and one in the left lobe.
ARTURO LOAIZA-BONILLA: Okay. Thank you so much for that. In terms of other clinical characteristics based on this profile, Frank has controlled hypertension, which is a factor that we always should consider when selecting treatment. So, in terms of clinical parameters defined in the IMbrave150 trial, let's look into what they define as an inadequately controlled arterial hypertension. They define it as a systolic blood pressure of at least 150 millimeters of mercury and/or a diastolic blood pressure of over 100 millimeters of mercury, all this based on an average of at least three readings of blood pressure in two different sessions. Okay, so based on Frank's chart, are his previously treated varices a concern? Why or why not? I think it's a good point now to discuss.
REENA SALGIA: Yeah, so this is an important question, and as we previously mentioned, patients with completely treated varices and without bleeding were eligible for enrollment in the IMbrave150 trial. So based on Frank's profile, he was screened for varices within six months and his varices were completely treated. In this trial, patients were required to be evaluated for the presence of varices within six months prior to treatment and varices of any size were assessed and treated as needed according to what would be the local standards of care. Patients in the IMbrave150 trial were assessed by esophagogastroduodenoscopy, or EDG. All patients must have undergone an EDG and all sizes of varices must have been assessed and treated per the local standards of care prior to enrollment.
ARTURO LOAIZA-BONILLA: Thank you for that. So an evaluation for the presence of varices is always recommended within six months of initiation of a [INDISCERNIBLE] new patient with HCC. It's important to note that there is a lack of clinical data to support the safety of Avastin in patients with variceal bleeding within six months prior to treatment, untreated, or incompletely treated varices with bleeding, or high risk of bleeding because these patients were excluded from clinical trials of Avastin in HCC. Dr. Salem, having reviewed Frank's profile, what additional information does Frank's CT scan reveal
RIAD SALEM: So you can see from Frank's CT scan that he has a cirrhotic liver. Additionally, Frank has two liver lesions, one in the left lobe and another one in the posterior sector of the right lobe, suggesting that he has multifocal bilobar disease. Both lesions measure approximately 6.5 centimeters in size. So basically, putting everything together, and Frank's CT scan confirms that he is a BCLC Stage B patient without vascular invasion
ARTURO LOAIZA-BONILLA: Thanks for that. So, after discussing Frank's CAT scans and his patient profile, let's think about why will Frank be eligible for Tecentriq and Avastin?
RIAD SALEM: Tecentriq and Avastin is the first FDA approved immunotherapy combination for first line unresectable and/or metastatic HCC in patients who have not received prior systemic therapy. Frank's profile indicates that he is a patient with unresectable HCC who has not previously received systemic therapy, suggesting that he may be eligible for Tecentriq and Avastin.
REENA SALGIA: Additionally, our patient, Frank, meets the eligibility criteria used for patients enrolled in the IMbrave150 study. Notably, he's a Child-Pugh A in regard to his liver function, meaning that he has adequate liver function. His tumor burden would be classified as Barcelona Stage B, or intermediate stage, and he had completely treated varices without bleeding. The multidisciplinary team, or MDT, should consider treatment options including local regional therapy for this patient, and if a patient is not a candidate for LRT, then consider the patient for Tecentriq and Avastin.
ARTURO LOAIZA-BONILLA: Well, I want to thank you for joining us today for this multidisciplinary roundtable discussion on a patient case in first line unresectable HCC. I want to thank the panelists as well for this enriching discussion and for going through all the data in the patient's profile. We hope that you found this discussion enlightening and informative to your practice.
SPEAKER 1: For serious adverse reactions, please refer to the full prescribing information for important dose management information specific to adverse reactions. Tecentriq is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 or the PD-ligand 1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.
[00:10:00]
Important immune-mediated adverse reactions listed under warnings and precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, they can also manifest after discontinuation of treatment. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. In general, if Tecentriq requires interruption or discontinuation, administer systemic corticosteroid therapy until improvement to Grade 1 or less. Then initiate corticosteroid taper and continue to taper over at least one month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Tecentriq can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune mediated pneumonitis occurred in 3 percent of patients receiving Tecentriq as a single agent, including fatal, Grade 4, Grade 3, and Grade 2 adverse reactions. Tecentriq can cause immune-mediated colitis. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal bleeding. Cytomegalovirus infection reactivation has been reported in patients with corticosteroid refractory immune-mediated colitis. In cases of corticosteroid refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Tecentriq can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.8 percent of patients receiving Tecentriq as a single agent, including fatal, Grade 4, Grade 3, and Grade 2 adverse reactions. Tecentriq can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Adrenal insufficiency occurred in 0.4 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Tecentriq can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect, such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Hypophysitis occurred in less than 0.1 percent of patients receiving Tecentriq as a single agent, including Grade 2 adverse reactions. Tecentriq can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or medical management for hyperthyroidism as clinically indicated. Thyroiditis occurred in 0.2 percent of patients receiving Tecentriq as a single agent, including Grade 2 adverse reactions. Hypothyroidism occurred in 4.9 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Initiate treatment with insulin, as clinically indicated. Type 1 diabetes mellitus occurred in 0.3 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions. Tecentriq can cause immune-mediated nephritis. Immune-mediated nephritis with renal disfunction occurred in less than 0.1 percent of patients receiving Tecentriq as a single agent and this adverse reaction was a Grade 3 adverse reactions. Tecentriq can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, DRESS, and toxic epidermal necrolysis has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated dermatologic adverse reactions occurred in 0.6 percent of patients receiving Tecentriq as a single agent, including Grade 3 and Grade 2 adverse reactions.
[00:15:00]
The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1 percent in patients who received Tecentriq or were reported with the use of other PD-1/PD-L1 blocking antibodies. Cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis, sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection. Tecentriq can cause severe or life-threatening infusion related reactions. Interrupt, slow the rate of, or permanently discontinue based on the severity. For Infusion related reactions occurred in 1.3 percent of patients, including Grade 3 reactions. Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogenic HSCT. Tecentriq can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating Tecentriq. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with Tecentriq and for at least five months after the last dose. The most common adverse reactions in patients who receive Tecentriq in combination with bevacizumab for HCC were hypertension, fatigue/asthenia, and proteinuria. Advise female patients not to breastfeed during treatment and for at least five months after the last dose. You may report side effects to the FDA at 1-800-FDA-1088, or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555. Please see the full prescribing information for additional important safety information.
1L=first line; HCC=hepatocellular carcinoma.
TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.
Severe and Fatal Immune-Mediated Adverse Reactions
TECENTRIQ is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. The following immune-mediated adverse reactions may not include all possible severe and fatal immune-mediated reactions.
Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting TECENTRIQ. While immune-mediated adverse reactions usually manifest during treatment with TECENTRIQ, they can also manifest after discontinuation of treatment. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of TECENTRIQ.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue TECENTRIQ depending on severity. In general, if TECENTRIQ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less, then initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
Immune-Mediated Colitis
Immune-Mediated Hepatitis
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
Hypophysitis
Thyroid Disorders
Type 1 Diabetes Mellitus, Which Can Present With Diabetic Ketoacidosis
Immune-Mediated Nephritis With Renal Dysfunction
Immune-Mediated Dermatologic Adverse Reactions
Other Immune-Mediated Adverse Reactions
Infusion-Related Reactions
Complications of Allogeneic HSCT After PD-1/PD-L1 Inhibitors
Embryo-Fetal Toxicity
Use in Specific Populations
Nursing Mothers
Fertility
Most Common Adverse Reactions
The most common adverse reactions (rate ≥20%) in patients who received TECENTRIQ in combination with bevacizumab for HCC were hypertension (30%), fatigue/asthenia (26%), and proteinuria (20%).
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see full TECENTRIQ Prescribing Information and full Avastin Prescribing Information for additional Important Safety Information.
TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.
Severe and Fatal Immune-Mediated Adverse Reactions
TECENTRIQ is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. The following immune-mediated adverse reactions may not include all possible severe and fatal immune-mediated reactions.
Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting TECENTRIQ. While immune-mediated adverse reactions usually manifest during treatment with TECENTRIQ, they can also manifest after discontinuation of treatment. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of TECENTRIQ.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue TECENTRIQ depending on severity. In general, if TECENTRIQ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less, then initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
Immune-Mediated Colitis
Immune-Mediated Hepatitis
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
Hypophysitis
Thyroid Disorders
Type 1 Diabetes Mellitus, Which Can Present With Diabetic Ketoacidosis
Immune-Mediated Nephritis With Renal Dysfunction
Immune-Mediated Dermatologic Adverse Reactions
Other Immune-Mediated Adverse Reactions
Infusion-Related Reactions
Complications of Allogeneic HSCT After PD-1/PD-L1 Inhibitors
Embryo-Fetal Toxicity
Use in Specific Populations
Nursing Mothers
Fertility
Most Common Adverse Reactions
The most common adverse reactions (rate ≥20%) in patients who received TECENTRIQ in combination with bevacizumab for HCC were hypertension (30%), fatigue/asthenia (26%), and proteinuria (20%).
You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see full TECENTRIQ Prescribing Information and full Avastin Prescribing Information for additional Important Safety Information.
TECENTRIQ Prescribing Information. Genentech, Inc.
TECENTRIQ Prescribing Information. Genentech, Inc.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.1.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed March 29, 2022. To view the most recent and complete version of the guideline, go online to www.NCCN.org.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.1.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed March 29, 2022. To view the most recent and complete version of the guideline, go online to www.NCCN.org.
Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-1905.
Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-1905.
Cheng A-L, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma.
J Hepatol. 2022;76:862-873.
Cheng A-L, Qin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma.
J Hepatol. 2022;76:862-873.
Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated efficacy and safety by risk status in patients (pts) receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment for unresectable hepatocellular carcinoma (HCC). Paper presented at: 2021 American Association for Cancer Research (AACR) Annual Meeting; April 10-15, 2021; virtual conference.
Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated efficacy and safety by risk status in patients (pts) receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) as first-line treatment for unresectable hepatocellular carcinoma (HCC). Paper presented at: 2021 American Association for Cancer Research (AACR) Annual Meeting; April 10-15, 2021; virtual conference.
Data on file. Clinical Study Report YO40245. Genentech, Inc.
Data on file. Clinical Study Report YO40245. Genentech, Inc.
Li D, Sedano S, Allen R, Gong J, Cho M, Sharma S. Current treatment landscape for advanced hepatocellular carcinoma: patient outcomes and the impact on quality of life. Cancers. 2019;11:841.
Li D, Sedano S, Allen R, Gong J, Cho M, Sharma S. Current treatment landscape for advanced hepatocellular carcinoma: patient outcomes and the impact on quality of life. Cancers. 2019;11:841.
Kudo M, Finn R, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet. 2018;391:1163-1173.
Kudo M, Finn R, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 noninferiority trial. Lancet. 2018;391:1163-1173.
Data on file. Study Protocol YO40245. Genentech, Inc.
Data on file. Study Protocol YO40245. Genentech, Inc.
Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:991-1001.
Galle PR, Finn RS, Qin S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:991-1001.
Data on file. Roche.
Data on file. Roche.
Avastin (bevacizumab) Prescribing Information. Genentech, Inc.
Avastin (bevacizumab) Prescribing Information. Genentech, Inc.
The information contained in this section of the site is intended for U.S. healthcare professionals only. Click "OK" if you are a healthcare professional.
The link you have selected will take you away from this site to one that is not owned or controlled by Genentech, Inc. Genentech, Inc. makes no representation as to the accuracy of the information contained on sites we do not own or control. Genentech does not recommend and does not endorse the content on any third-party websites. Your use of third-party websites is at your own risk and subject to the terms and conditions of use for such sites.