Abstract 52P
Background
For many systemic treatments in oncology, a divergence between efficacy in clinical trials versus effectiveness in clinical practice has been observed. The present study investigated the real-world outcomes for pembrolizumab plus chemotherapy in patients with stage IV non-squamous non-small cell lung cancer (NSCLC) and compared these with the results of the KEYNOTE-189 trial.
Methods
This retrospective cohort study included all patients diagnosed with stage IV non-squamous NSCLC and treated with first-line pembrolizumab plus pemetrexed-platinum in 2019 and 2020 within a network of seven teaching hospitals (Santeon) in the Netherlands. The overall survival observed in the real-world was compared with the KEYNOTE-189 trial by calculating hazard ratios (HR) with 95% confidence intervals (95%CI) for the total population and PD-L1 subgroups.
Results
A total of 512 patients were included (median age 65 years, 49% males; 9% ECOG-PS 2, and 19% with brain metastasis). The median OS (mOS) was shorter in clinical practice than in the trial (13 vs 22 months) with a HR (95%CI) of 1.50 (1.26–1.79) (table). The divergence from the trial was most pronounced in patients with <1% PD-L1 expression (mOS 10 vs 17 months; HR 1.38, 95%CI 1.06–1.79). Early discontinuation of chemotherapy (<4 cycles platinum) was more frequent in the real-world than the trial (35 vs 18%).
Table: 52PThe overall survival for stage IV non-squamous patients treated with pembrolizumab plus chemotherapy (real-world vs KEYNOTE-189)
| Real-world vs KEYNOTE-189 | ||
|---|---|---|
| mOS in months (n) | HR (95%CI) for OS | |
| Total population | 13 (512) vs 22 (410) | 1.50 (1.26–1.79) |
| PD-L1 subgroups | ||
| PD-L1 <1% | 10 (269) vs 17 (127) | 1.38 (1.06–1.78) |
| PD-L1 ≥1–49% | 20 (158) vs 22 (128) | 1.10 (0.80–1.51) |
| PD-L1 ≥50% | 26 (59) vs 28 (132) | 1.21 (0.76–1.89) |
| Unknown | 9 (26) vs NA (23) | NA |
Conclusions
This study showed considerably worse real-world mOS for pembrolizumab plus chemotherapy compared to the corresponding clinical trial. In patients with low PD-L1 expression, the benefit of pembrolizumab added to chemotherapy seems limited.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.