Updated results from the phase III KEYNOTE-407 study reported at the European Lung Cancer Virtual Congress 2021 (25-27 March) demonstrated that survival and response rates remained improved with pembrolizumab plus chemotherapy over placebo plus chemotherapy in treatment-naive patients with metastatic squamous non-small cell lung cancer (NSCLC).
Andrew G. Robinson of the Cancer Centre of Southeastern Ontario at Kingston General Hospital in Kingston, Canada presented long-term findings from the KEYNOTE-407 study (NCT02775435) including in patients who received up to 35 cycles or approximately 2 years of pembrolizumab.
A prior report from the protocol-specified final analysis in May 2019 showed that patients with previously untreated metastatic squamous NSCLC receiving pembrolizumab plus carboplatin together with paclitaxel or nab-paclitaxel had significantly improved overall survival (OS) compared to those receiving only chemotherapy (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.58–0.88).
The randomised, double-blind, phase III KEYNOTE-407 study compared pembrolizumab at 200 mg plus chemotherapy in 278 patients versus placebo plus chemotherapy in 281 patients every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles. Chemotherapy consisted of carboplatin plus a taxane (paclitaxel or nab-paclitaxel). The patients were stratified according to paclitaxel versus nab-paclitaxel, East Asia versus rest of the world, and PD-L1 tumour proportion score (TPS) ≥1% versus <1%.
The primary endpoints of this study were OS and progression-free survival (PFS) per RECIST v1.1 by blinded independent central review.
Patients completing 35 pembrolizumab cycles showed the most improved outcomes
On 30 September 2020, the median time from randomisation to data cutoff was 40.1 (range, 33.1 to 49.4) months. By this time, 143 (51.1%) patients had crossed over from the placebo/chemotherapy arm to receive either pembrolizumab monotherapy on study or received another anti−PD-(L)1 therapy.
OS was improved with the addition of pembrolizumab to chemotherapy; median OS with pembrolizumab/chemotherapy was 17.2 compared to 11.6 months with placebo/chemotherapy (HR 0.71; 95% CI 0.59−0.86). Three-year OS rates of 29.7% versus 18.2% were observed with pembrolizumab/chemotherapy versus placebo/chemotherapy, respectively.
The median PFS was also improved with the addition of pembrolizumab to chemotherapy, 8.0 versus 5.1 months (HR 0.59; 95% CI 0.49−0.71); the 3-year PFS rates were 16.1% with pembrolizumab versus 6.5% with placebo. In the respective treatment groups, median PFS2 was 13.8 versus 9.1 months (HR 0.59; 95% CI 0.49−0.71).
Adding pembrolizumab to chemotherapy improved the objective response rate (ORR) to 62.6% compared to 38.8% with placebo/chemotherapy and the median duration of response was 9.0 (range, 1.3+ to 45.0+) months compared to 4.9 (range, 1.3+ to 44.8+) months, respectively.
Among the 55 patients completing 35 cycles of pembrolizumab, the ORR was 92.7%, which included 5 patients with complete response and 46 with partial response; 4 (7.3%) patients had stable disease. After completion of 35 pembrolizumab cycles, 51 (92.7%) patients were alive. The 1-year OS and PFS rates from completion of pembrolizumab were 96.0% and 82.6%, respectively. As of data cut-off, 7 patients had initiated a second course of pembrolizumab.
The incidence of Grade 3−5 adverse events was similar in both arms, at 74.8% with pembrolizumab/chemotherapy and 70.0% with placebo/chemotherapy.
Based upon these findings, the authors concluded that pembrolizumab plus chemotherapy continued to demonstrate durable benefit with >3 years of follow-up as compared to placebo plus chemotherapy, without additional toxicity.
They noted that the majority of patients completing 35 cycles showed objective responses and were alive at data cut-off.
According to the authors, these long-term data continue to support pembrolizumab plus chemotherapy as first-line treatment in patients with metastatic squamous NSCLC.
This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
97O - Robinson AG, Vicente D, Tafreshi A, et al. First-Line Pembrolizumab Plus Chemotherapy for Patients With Advanced Squamous NSCLC: 3-Year Follow-up From KEYNOTE-407. European Lung Cancer Virtual Congress 2021 (25-27 March).