Lack of patient selection holds back new combinations in melanoma

Targeted therapies have delivered on their promise to make oncology more personalized. However, the addition of immunotherapy agents without first testing for patients who are most likely to benefit may limit the success of triplet combinations in melanoma, says GlobalData, a leading data and analytics company.

The addition of Tecentriq (atezolizumab) to a doublet therapy consisting of Zelboraf (vemurafenib) and Cotellic (cobimetinib), all marketed by Roche, led to a significant improvement in progression-free survival (PFS) over the doublet therapy alone in the IMspire150 Phase III study. Despite this positive outcome, its positioning in the treatment sequence is uncertain, says GlobalData, a leading data and analytics company.

Sakis Paliouras, PhD, Oncology and Hematology Analyst at GlobalData, says: “Results of the IMspire150 trial strongly suggest that a subset of melanoma patients derive great benefit from the addition of Tecentriq to doublet therapy. However, further biomarker testing is needed to specifically identify those populations. Moreover, the question of whether immunotherapy should be used upfront or reserved for subsequent lines of therapy in BRAF-mutant melanoma remains unanswered.

The addition of Tecentriq led to a significant improvement of 4.5 months in PFS over the doublet regimen. Interestingly, the median duration of response was 21 months for the triplet vs 12.6 months for the doublet regimen.

Paliouras continued: “A high standard set by the blockbuster combination of Yervoy + Opdivo, which has been shown to offer over 50% five-year overall survival, will result in uncertain adoption of new agents in the first-line treatment of metastatic melanoma. Competition is expected to rise further with the introduction of more immunotherapy agents. However, without proper patient selection, the addition of immunotherapy to doublet regimens is only warranted to create more uncertainty in the treatment paradigm. Key opinion leaders interviewed by GlobalData have agreed that triplet therapies are important for first-line therapy in BRAF-mutant melanoma. However, without head-to-head testing with the most aggressive regimen they will be uncertain about how to choose the most effective therapy.”

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