Toxicities and Duration of Treatment for Immunotherapy in Advanced HCC

Namrata Vijayvergia, MD, Gastrointestinal Medical Oncology, Fox Chase Cancer Center, and Christopher Lieu, MD, Gastrointestinal Medical Oncology, University of Colorado, conclude their discussion with considerations for managing immunotherapy-related toxicities in patients with metastatic hepatocellular carcinoma (HCC), along with a review of the available evidence regarding duration of immunotherapy treatment.

Dr. Lieu: With immunotherapy, there is significant opportunity, aiming for that durable response. However, we are also aware of specific toxicities associated with immunotherapy. Could you share your approach to managing immunotherapy-related toxicity in patients with HCC?

Dr. Vijayvergia: Absolutely, and another aspect to consider is the duration of treatment. It is exciting to have discussions about these topics now, which were not prevalent before. While immunotherapy-related side effects are generally milder compared to TKIs, they can be serious for some patients. For durva/treme, there is about a 35-40% rate of grade 3 adverse events, mostly occurring in the first 3 months. If patients do well in this initial period, they usually continue without further issues. Atezo/bev has early side effects too, particularly related to bevacizumab, such as hypertension and bleeding.

Addressing thyroiditis and endocrine issues is crucial. Fatigue, a common complaint, often stems from underlying thyroid problems, easily treatable once identified. Monitoring for immunotherapy-related hepatitis is challenging but necessary, as sudden changes require attention. Fortunately, effective treatment options, including new drugs and steroids, are available for managing these side effects. Although rare, colitis in the GI and hepatic side effects are concerns I prioritize.

Dr. Lieu: I completely agree. Early identification and prompt cessation of therapy contribute to better outcomes.

Dr. Vijayvergia: Regarding the duration of treatment, both the IMbrave trial and HIMALAYA study allowed patients to continue treatment until progression. In our practice, we have seen patients stable for up to 2 years without progression. While conventional teaching suggests withdrawing immunotherapeutic drugs after 2 years if stability is maintained, it lacks supporting data. Have you considered this for your patients?

Dr. Lieu: Absolutely, it is a fascinating conversation to have. Occasionally, we encounter exceptional responders with complete radiographic responses or significant changes in tumor character. Around the two-year mark, discussions with patients revolve around the necessity of ongoing therapy. Some patients are hesitant to address this topic, and physicians are no exception. Two strategies emerge — if a patient tolerates therapy well, and all is stable, continuing without interruption is reasonable. However, considering the expense, time commitment, and potential side effects, a cessation of therapy, followed by close surveillance through imaging, can be a viable option. It is crucial to evaluate for any changes during this break. What is your approach in your practice?

Dr. Vijayvergia: I am relieved to hear that it aligns with what I have been doing. When evidence is lacking, a cautious withdrawal of therapy is a common approach. For some patients experiencing side effects like fatigue or hypertension, a break can lead to improvement. However, for those tolerating therapy well, I often adopt a “let’s not rock the boat” approach, considering the absence of concrete evidence.

Dr. Lieu: It is reassuring to know that our practices align, and the cautious withdrawal strategy is a common thread. Individualizing decisions based on patient response and potential side effects is essential in the absence of conclusive evidence.

View their previous conversations, including Analyzing the Immunotherapy Landscape for Advanced HCC and Biomarkers of Response and Sequencing for Immunotherapy in Advanced HCC.