First-line pembrolizumab monotherapy offers durable OS benefit vs chemotherapy in NSCLC patients with high PD-L1 expression

It has been shown after a follow-up of more than 3 years that first-line pembrolizumab monotherapy provides durable long-term overall survival (OS) compared to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). This OS benefit was observed despite 65% of patients assigned to chemotherapy crossing over to pembrolizumab. Furthermore, pembrolizumab had a manageable long-term safety profile.

Dr Martin Reck (Lung Clinic Grosshansdorf, Germany) presented data on 3-year survival from the KEYNOTE-024. Patients with advanced NSCLC who had programmed death-ligand 1 (PD-L1) ≥50% and who had no targetable epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) alterations had been randomised to pembrolizumab or platinum-based chemotherapy. Earlier results had already shown that first-line pembrolizumab significantly improved progression-free survival (PFS) as well as OS compared with chemotherapy [1].

For this longer follow-up (mean length of follow-up was 44.4 months), patients were randomised to pembrolizumab 200 mg for 2 years (n=154) or platinum doublet (n=151) for 4 to 6 cycles plus optional pemetrexed maintenance (non-squamous), with stratification by Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1, tumour histology (squamous/non-squamous), and region (East Asia/non-East Asia). Patients in the chemotherapy arm could cross over to pembrolizumab upon disease progression if they met eligibility criteria. The primary endpoint was PFS, whilst OS was a key secondary endpoint [2].

The results demonstrated that median OS for pembrolizumab was over a year longer compared with chemotherapy (26.3 vs 14.2 months); the 36-month OS was 43.7% in the pembrolizumab arm vs 24.9% in the chemotherapy arm. Interestingly, although patients on pembrolizumab had a longer mean treatment duration than those on chemotherapy (11.1 vs 4.4 months, respectively), grade 3-5 treatment-related adverse events occurred less frequent with pembrolizumab vs chemotherapy (see Figure).

Figure. Treatment exposure and AEs in the overall population [2]

1.  Reck M, et al. N Engl J Med. 2016;375:1823-1833.
2.  Reck M, et al. OA07.01. WCLC 2019.

Posted on 8 November 20194 September 2023