Background and importance Pembrolizumab monotherapy (Pb) showed benefit in terms of overall survival (OS) and progression free survival (PFS) compared with chemotherapy alone (CT) in untreated metastatic non-small cell lung cancer (mNSCLC) with PD-L1 ≥50% expression. The Pb-CT combination presented benefit in terms of OS and PFS in untreated metastatic squamous NSCLC (mSNSCLC), regardless of PD-L1 expression. No randomised clinical trials (RCTs) of Pb-CT versus Pb alone have been done.
Aim and objectives To assess the comparative efficacy of Pb and Pb-CT in untreated mSNSCLC patients with PD-L1 ≥50% using an adjusted indirect treatment comparison (ITC).
Material and methods A bibliographic search was conducted in the Pubmed database (2 October 2019). Inclusion criteria were phase III RCTs, Pb and Pb-CT treatments, similar mSNSCLC population (with PD-L1 ≥50%), follow-up period and end points(OS or PFS). Exclusion criteria were mSNSCLC population with EGFR or ALK mutations. An ITC was developed using Bucher’s method. Delta value (Δ), maximum acceptable difference as a clinical criterion of no inferiority, was set at 0.70 (and its inverse, 1.43), used to calculate the sample size in the Pb-CT trial. The Shakespeare method was used to estimate the probability of the results out of the Δ margins.
Results Two studies, one for each regimen,1 2 were found in the literature search. Limitations found between Pb-CT and Pb trials included populations (all patients vs only patients with PD-L1 ≥50%, respectively, subgroup data used for ITC) and small size of the squamous subgroup. No OS data were available for the squamous subgroup in the Pb trial. PFS was taken as the primary end point for ITC. Results of RCTs and ITC are shown in table 1.
No significant differences in PFS between Pb-CT and Pb were found. The 95% CI exceeded Δ on both sides (high level of uncertainty). The probability of a result out of Δ were 24.14% below and 16.54% above.
Conclusion and relevance ITC did not show significant differences in PFS between Pb-CT and Pb. No evidence of clinically relevant benefit from one or other regimen was found. Considering the toxicity related to the addition of CT, Pb monotherapy would be preferable in untreated mSNSCLC with PD-L1 ≥50%.
References and/or acknowledgements 1. Paz-Ares L, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018;379:2040–2051.
2. Reck M, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823–1833.
No conflict of interest.
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