- •Treatment sequencing is a viable option for NSCLC with a PD-L1 expression ≥ 50%.
- •Post-progression pathways of a cohort of NSCLC receiving pembrolizumab were reported.
- •Post-progression outcomes are major determinants for worse clinical outcomes.
- •Our results should be considered when counselling patients for first-line choices.
Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%.
We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy.
Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients’ features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148).
In the real-world scenario NSCLC patients with PD-L1 expression ≥50% treated with first-line single-agent pembrolizumab achieve worse outcomes as compared to the Keynote-024 trial. Poor post-progression outcomes are major determinants of the global results that should be considered when counselling patients for first-line treatment choices.
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Published online: March 12, 2021
Accepted: February 11, 2021
Received in revised form: February 6, 2021
Received: November 27, 2020
© 2021 Elsevier Ltd. All rights reserved.
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- Re: Post-progression outcomes of NSCLC patients with PD-L1 expression ≥50% receiving first-line single-agent pembrolizumab in a large multicentre real-world studyEuropean Journal of CancerVol. 155
- PreviewWe read a very interesting article by Cortellini et al. in which they compared treatment regimens used in the progression that develops after pembrolizumab monotherapy in patients with PD-L1 >50% . A standard recommendation is to use immunotherapies as first-line treatment in a PD-L1-positive patient. In addition, current data in the literature regarding the continuation of immunotherapy agents during progression is deficient.