Key Takeaways From ESMO: Updates on Immunotherapy for Melanoma
PracticeUpdate: There was some key data on immunotherapy for metastatic melanoma presented at this year's ESMO. Could you describe some of the most relevant findings?
Dr. Dronca: What we've learned in the last decade in the treatment of metastatic melanoma is that, really, immunotherapy and targeted therapy remain the cornerstones of treatment and have significantly changed and improved the overall survival of patients, with more than 50% now showing significant clinical benefit. Immunotherapy, with immune checkpoint inhibitors, anti-CTLA-4, and, anti-PD-1 and PD-L1 agents, has played a significant role in the treatment of melanoma and now in the treatment of other cancers.
One of the major studies presented at ESMO this year looked at the dynamic of response as well as depth of response to immune checkpoint inhibitor in metastatic melanoma. The study was presented by Dr. Caroline Robert and looked at patients who achieved a complete response to a combination of ipilimumab/nivolumab or nivolumab in three large clinical studies, [CheckMate] 069, 067, and 066. What we learned is that a very high number of patients achieved a complete response, 20% approximately on both groups, which is very impressive for this patient population considering the responses seen with immune checkpoint therapy in other malignancies.
PracticeUpdate: Was this complete response predictive of long-term outcomes?
Dr. Dronca: Furthermore, the authors have looked at patients who achieved a complete response within the first 12 months of treatment and found that this indeed seems to be predictive of a long-term relapse-free survival and overall survival with more than 80% of patients, both in the ipilimumab/nivolumab group as well as nivolumab group being alive at 5 years. Patients achieving a partial response in the first 12 months seemed to still have clinical benefit with around 60% of patients being around at 5 years.
PracticeUpdate: How would this impact clinical practice?
Dr. Dronca: This potentially can have significant implications both in clinical practice and treatment decisions. How long do we continue therapy and how do we monitor and follow patients who achieve a robust response, especially early on, to anti-PD-1 therapy. It could also help design studies, I believe, that look at biomarkers of response. I took this as an important confirmation of the robust response of anti-PD-1 therapy and anti-CTLA-4 therapy in patients with metastatic melanoma, and definitely dynamic of response matters.
Other things that we've learned, I believe, is that treatment of patients who fail immune checkpoint inhibitors remains a very large unmet need in this patient population. While the responses happen in a significant number of patients upfront, about 50%, still there are patients who do not respond to therapy, patients who progress upon initiation of anti-PD-1 therapy, and these remain major challenges in the clinic for the treating oncologist.
PracticeUpdate: Was there any data presented at ESMO that might help address the needs of these relatively less responsive patients?
Dr. Dronca: Therefore, multiple combinations, immunotherapy combinations, have been studied in the space with some of them presented at ESMO this year. A major study looked at lenvatinib, which is a multiple TKI inhibitor in patients who have failed anti-PD-1 therapy. Lenvatinib is believed to positively modulate the immune microenvironment by both VEGF as well as FGFR inhibition. In an early study, lenvatinib was shown to have an impressive response of around 47% and in this follow-up study, LEAP-004, presented at ESMO this year, it showed that the efficacy is maintained with a response of around 20% in patients who previously failed anti-PD-1 therapy, which again is a very difficult patient population to treat. This combination remains definitely a possibility of therapy in the future in combination therapy.
PracticeUpdate: What other combinations were presented at ESMO this year?
Dr. Dronca: Another treatment explored was a TLR9 agonist, tilsotolimod, in combination with anti-PD-1 therapy, again in patients who have failed a prior immune checkpoint inhibitor.
Other studies explored involved a dendritic cell vaccine in anti-PD-1 naïve patients, which again showed positive immune modulation and possible treatment in the future in the combination therapy. One of the studies looked at a novel anti-PD-1 therapy, spartalizumab, in combination with targeted therapy with dabrafenib and trametinib.
While the study did not meet its endpoint, we learned that this combination actually is effective in melanoma, and currently a similar combination is approved in the United States and therefore, further analysis of the statistical design as well as the patient characteristics at enrollment, and long-term follow-up, are needed to explore whether combination of targeted therapy and immunotherapy indeed results in longer and more sustained clinical benefit in patients with metastatic melanoma.
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