Background Pembrolizumab (Pb) showed significant benefit in overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with untreated metastasic non-small-cell lung cancer (NSCLC) and ≥50% PD-L1 expression. The pembrolizumab-chemotherapy combination (Pb-CT) also showed significant benefit in OS and PFS over chemotherapy in patients with untreated non-squamous NSCLC, regardless of PD-L1 value. It lacks clinical trials of Pb-CT vs. Pb alone.
Purpose To develop an adjusted indirect treatment comparison (ITC) between Pb and Pb-CT in non-squamous NSCLC with PD-L1 ≥50%.
Material and methods A bibliographic search was conducted to select phase III randomised clinical trials with Pb and Pb-CT in a similar non-squamous NSCLC population (without EGFR or ALK mutations and PD-L1 ≥50%), follow-up period and endpoints. ITC was elaborated using Bucher’s method with hazard ratio (HR) and 95% CI.
Results Two trials were selected, one of each regimen. Limitations found: differences in control treatment – platin doublets with pemetrexed vs. several drugs (pemetrexed subgroup was selected for PFS comparison; subgroup data lack for OS comparison) – masking (double-blind vs. open-label design), included population (only patients with PD-L1 ≥50% vs. all patients, then subgroup data were used; and inclusion of 18% patients with squamous tumour). The follow-up period of Pb and Pb-CT trials were 11.2 and 10.5 months, respectively. The results of pivotal trials and ITC are shown below:
Significant differences in PFS between Pb-CT and Pb results were observed. No significant differences in OS results were found (broad 95% CI with a high level of uncertainty).
Conclusion Pb-CT showed benefit in PFS over Pb monotherapy for patients with non-squamous NSCLC and ≥50% PD-L1 expression receiving pemetrexed combinations. Overall survival benefit is doubtful because of potential bias and large 95% CI. Monotherapy Pb reserves platinum doublet for later use, and additional data for OS in the pemetrexed subgroup is needed for addressing the benefit of the combination. Taking into account the toxicity of adding chemotherapy, the combined regimen should be considered cautiously.
References and/or acknowledgements None.
No conflict of interest.