Then in August, the PD-1 inhibitor nivolumab was approved as a single agent for metastatic small cell lung cancer (SCLC) following progression on platinum-based chemotherapy and at least one other line of therapy.
The approval is based on the durability of responses in the phase I/II CheckMate-032 trial, in which the ORR was 12% (95% CI, 6.5-19.5) for nivolumab following platinum-based chemotherapy and one other prior line. The median DoR was 17.9 months, with 62% of patients continuing to respond at 12 months. This was the first approval in SCLC in nearly 20 years.
Checkpoint inhibitor approvals continued in lung cancer this year with an indication for pembrolizumab, another PD-1 inhibitor in chemotherapy combinations in the first-line for both squamous and non-squamous NSCLC.
In late August of this year, the FDA granted a full approval to frontline pembrolizumab in combination with platinum-based chemotherapy plus pemetrexed for patients with non-squamous NSCLC, based on findings from the phase III KEYNOTE-189 trial. In this trial, the addition of pembrolizumab to pemetrexed and either cisplatin or carboplatin reduced the risk of death by 51%. At the time of approval, the median overall survival (OS) had not been reached with pembrolizumab compared with 11.3 months in the chemotherapy-alone arm. The estimated 12-month OS rate was 69.2% in the immune-chemotherapy combination arm compared with 49.4% for chemotherapy alone.
Then at the end of October, the FDA approved first-line use of pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel for the treatment of patients with metastatic squamous NSCLC, based on results from the phase III KEYNOTE-407 trial. Here, pembrolizumab plus chemotherapy reduced the risk of death by 36% compared with chemotherapy alone in patients with metastatic disease. The median OS was 15.9 months with pembrolizumab versus 11.3 months with chemo alone Overall survival benefit was observed regardless of PD-L1 expression level, choice of chemotherapy, age, sex, or performance status.
In late September, the FDA approved dacomitinib for the frontline treatment of patients with metastatic EGFR-mutated NSCLC based on the phase III ARCHER 1050 trial. Investigators showed, dacomitinib resulted in an average 6.5-month improvement in response duration compared with gefitinib as a first-line treatment.
The median PFS was 14.7 months on dacomitinib compared with 9.2 months on gefitinib. The median DoR was 14.8 months versus 8.3 months, respectively.
Approvals for targeted therapies continued through the Fall with lorlatinib for the treatment of patients with ALK-positive metastatic NSCLC who have progressed following one or more ALK TKIs. Specifically following crizotinib and at least one other ALK inhibitor for metastatic disease or either alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
This approval was based on a nonrandomized, dose-ranging, phase II study that included a subgroup of 215 patients with ALK-positive metastatic NSCLC previously treated with one or more ALK kinase inhibitors. The ORR with lorlatinib in these patients was 48% including a complete response rate of 4%. The median DoR was 12.5 months.
Finally, in early December, the PD-L1 inhibitor atezolizumab was approved for use in combination with bevacizumab, carboplatin, and paclitaxel for the first-line treatment of patients with metastatic non-squamous NSCLC without a sensitizing mutation.
The approval is based on findings from the phase III IMpower150 trial, in which the combination regimen reduced the risk of death by 22% compared with bevacizumab and chemotherapy.
Additionally, the median OS with the addition of atezolizumab was 19.2 months compared with 14.7 months in the control arm.