The year 2017 was one of prolific research and advancements. Repeatedly throughout the year, key results were announced from multiple trials investigating groundbreaking strategies emerged with practice-changing implications. The advent of checkpoint inhibitors continues to revolutionize the way we can treat our patients, and exploring their utility in multiple lines of therapy continued this past year.
In September, Borghaei and colleagues presented data at the ESMO 2017 Congress, confirming and expanding on previously published results of the KEYNOTE-021 trial investigating pembrolizumab (a PD-1 inhibitor) in combination with pemetrexed and carboplatin as a first-line therapy for patients with advanced nonsquamous NSCLC. Again, results demonstrated improved progressionfree survival (PFS) and objective response rate (ORR) for patients receiving the checkpoint inhibitor in combination with chemotherapy, compared to chemotherapy alone. Most recent results showed PFS was more than doubled for patients on the combination, with a reduced risk of progression of 46%. Then, it was then announced in January of this year that KEYNOTE-189, the phase III trial investigating this combination in metastatic NSCLC had reached its dual primary endpoints, demonstrating significantly improved overall survival (OS) and PFS for pembrolizumab plus chemotherapy. Full results of this trial are expected later this year.
Back in October 2017, results from the CheckMate-032 trial investigating the immunotherapy combination of nivolumab and ipilimumab for patients with small cell lung cancer with various levels of tumor mutation burden (TMB) were presented at 18th World Conference on Lung Cancer. Investigators showed patients with high TMB responded to the combination 46% of the time, but only 16% or 22% of patients with low and medium TMB responded, respectively. Investigators followed these results in February of this year, showing in the CheckMate-227 study that the dual immunotherapy combination achieved superior PFS in the first-line treatment of patients with NSCLC.
In November of last year, we saw Antonia and colleagues publish results from the phase III PACIFIC trial in the New England Journal of Medicine, showing that the PD-L1 inhibitor durvalumab had a superior PFS and ORR to placebo for patients with stage III NSCLC who had previously received chemoradiotherapy. Investigators showed administration of durvalumab reduced the risk of progression or death by 48% in these patients.
Then, in December, at the ESMO Immuno Oncology Congress 2017, Reck and colleagues demonstrated the efficacy of another checkpoint inhibitor combination strategy in NSCLC, this time atezolizumab (a PD-L1 inhibitor) in combination with chemotherapy and bevacizumab for stage IV disease. The phase III Impower150 trial demonstrated improved PFS for this combination, with OS data yet to be reported.