Charles Sawyers, MD
“The hypothesis of combining kinase inhibitors with checkpoint inhibitors could be a fantastic idea,” said formal study discussant Charles Sawyers, MD, of Memorial Sloan Kettering Cancer Center, New York. “This trial [IMspire150] is positive, and that is great news. Triple therapy is superior to kinases alone. The durability of the tail of the progression-free survival curve is most impressive, as expected. The investigators will need to sort out the discrepancy between the investigator assessment of progression-free survival and the central review.”
According to Dr. Sawyers, the control arm in this trial may no longer be relevant. The standard of care for advanced melanoma appears to be shifting to a checkpoint inhibitor (ie, nivolumab) plus a cytotoxic T-lymphocyte–associated protein 4 inhibitor (ie, ipilimumab).
“To me, the biggest question is why the combination therapy [ie, plus atezolizumab] is better. Perhaps the targeted agents prime the microenvironment for immunotherapy, changing the tumor from ‘warm’ to ‘hot.’ It is also possible that the benefit of combination therapy is due to patient-to-patient variability without drug activity or synthesis; that is, the benefit is actually due to the fact that some patients respond well to drug A and some to drug B. Time will tell,” commented Dr. Sawyers.
DISCLOSURE: Dr. Sawyers reported financial relationships with Novartis, ORIC Pharmaceuticals, Agios, BeiGene, Blueprint, Column Group, Foghorn, Housey Pharma, Nextech, KSQ Therapeutics, Petra, and PMV Pharmaceuticals.
The addition of the checkpoint inhibitor atezolizumab to two targeted therapies (the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib) as initial therapy improved outcomes compared with the two targeted therapies plus placebo in patients with newly diagnosed BRAF V600E/K–mutant advanced ...