Checkpoints at Every Turn

OncLive Chairman,

Mike Hennessy

Over the last month or so, the immune checkpoint blockade revolution in oncology has officially hit a fever pitch. From regulatory approvals and milestones to the release of the latest positive data, success with checkpoint agents continues its rapid advance across tumor types to nearly every corner of cancer care.

The FDA recently approved the PD-1 inhibitor pembrolizumab (Keytruda) for patients with pretreated, PD-L1—positive advanced non–small cell lung cancer. The regulatory agency also expanded the NSCLC approval of the anti—PD-1 agent nivolumab (Opdivo), adding a nonsquamous indication to the previously authorized use for squamous patients. Also in lung cancer, data presented at the 2015 World Conference on Lung Cancer showed that adding the PD-L1 inhibitor atezolizumab to chemotherapy improved responses in the frontline setting for patients with metastatic NSCLC. Atezolizumab has also shown efficacy as a single-agent in patients with pretreated advanced NSCLC, according to results from two pivotal phase II studies presented at the 2015 European Cancer Congress (ECC).

Combining checkpoint agents is also a key strategy going forward, with a regimen of nivolumab plus the CTLA-4 inhibitor ipilimumab (Yervoy) demonstrating frontline activity in advanced NSCLC, according to early data presented at the World Lung meeting. The FDA recently approved the combination of nivolumab and ipilimumab as a treatment for patients with BRAF V600 wild-type unresectable or metastatic melanoma. There have also been significant recent developments with checkpoint agents in the genitourinary setting. Nivolumab received an FDA breakthrough therapy designation for the treatment of patients with advanced renal cell carcinoma. Studies presented at the 2015 ECC showed positive clinical activity for atezolizumab and another anti—PDL1 agent, avelumab, in patients with metastatic urothelial carcinoma. The checkpoint juggernaut is also starting to reach blood cancers. Although the research is early, there is a potentially significant role for immune checkpoint inhibition in the treatment of lymphoma, according to a discussion at the recent 2015 Society of Hematologic Oncology (SOHO) annual meeting.

It’s important to note that there is still much work to be done on the immuno-oncology front—reliable biomarkers and companion diagnostics are absolutely essential to ensuring that the greatest number of patients are receiving the greatest possible benefit from these agents. Payer issues will also have to be resolved, given the high cost of these drugs, especially when used in combination regimens.

However, even with these challenges, there is no denying that the immune checkpoint blockade revolution has changed the course of oncology. The miraculous advances with these agents in the past 5-plus years alone is a true testament to the passion and innovative spirit you bring to the lab and/ or clinic. We at Oncology & Biotech News can’t wait to see what frontiers the great immuno-oncology journey takes us to next.