Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study. (May 2021)

• Record Type: Journal Article
• Authors: Cortellini, Alessio; Cannita, Katia; Tiseo, Marcello; Cortinovis, Diego L.; Aerts, Joachim G.J.V.; Baldessari, Cinzia; Giusti, Raffaele; Ferrara, Miriam G.; D'Argento, Ettore; Grossi, Francesco; Guida, Annalisa; Berardi, Rossana; Morabito, Alessandro; Genova, Carlo; Antonuzzo, Lorenzo; Mazzoni, Francesca; De Toma, Alessandro; Signorelli, Diego; Gelibter, Alain; Targato, Giada; Rastelli, Francesca; Chiari, Rita; Rocco, Danilo; Gori, Stefania; De Tursi, Michele; Mansueto, Giovanni; Zoratto, Federica; Filetti, Marco; Bracarda, Sergio; Citarella, Fabrizio; Russano, Marco; Cantini, Luca; Nigro, Olga; Buti, Sebastiano; Minuti, Gabriele; Landi, Lorenza; Ricciardi, Serena; Migliorino, Maria R.; Natalizio, Salvatore; Simona, Carnio; De Filippis, Marco; Metro, Giulio; Adamo, Vincenzo; Russo, Alessandro; Spinelli, Gian P.; Di Maio, Massimo; Banna, Giuseppe L.; Friedlaender, Alex; Addeo, Alfredo; Pinato, David J.; Ficorella, Corrado; Porzio, Giampiero;
• Is Part Of: European journal of cancer. Volume 148(2021)
• Page Start: 24
• Page End: 35
• Publication Date: 2021-05
• Subjects: Non-small cell lung cancer -- Immunotherapy -- PD-L1 -- Pembrolizumab -- Performance status -- Post-progression -- Radiotherapy -- Radiation therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.02.005
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. Methods: 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. Results: 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). Conclusions: 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. Highlights: 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.