First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study.

The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions. This was a French retrospective multicenter longitudinal study of 108 consecutive patients with advanced NSCLC, a PD-L1 TPS ≥50% and without EGFR/ALK aberrations who were treated by pembrolizumab, in first line. Patient data were obtained from medical files. The main characteristics of the cohort were: median age [range] 66.7 [37-87] years, 64.8% male, 23.1% with a performance status (PS) of 2, and 88.9% current or former smokers. Eighty-seven percent had stage IV NSCLC at diagnosis, 9.2% untreated brain metastases at inclusion,. With a median follow-up of 8.2 months, the median PFS was 10.1 months (95% CI, 8.8-11.4). The objective response rate was 57.3% (complete response 2.7%, partial response 54.6%). Disease control rate was 71.1%. At 6 months, the OS rate estimated was 86.2%. Treatment-related adverse events (AE) of grade 3 occurred in 8% of patients. There were no grade 4 or 5 AEs. In a real-life cohort of advanced NSCLC patients (including PS 2 and untreated brain metastases), with PD-L1 TPS ≥50%, pembrolizumab demonstrates similar PFS to the pivotal clinical trial.

Amrane K ，Geier M ，Corre R ，Léna H ，Léveiller G ，Gadby F ，Lamy R ，Bizec JL ，Goarant E ，Robinet G ，Gouva S ，Quere G ，Abgral R ，Schick U ，Bernier C ，Chouaid C ，Descourt R ... -  《Cancer Medicine》

Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1-positive advanced non-small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies.

Most lung cancer diagnoses occur in elderly patients, who are underrepresented in clinical trials. We present a pooled analysis of safety and efficacy in elderly patients (≥75 years) who received pembrolizumab (a programmed death 1 inhibitor) for advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1)‒positive tumors. The pooled analysis included patients aged ≥18 years with advanced NSCLC with PD-L1-positive tumors from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies. In KEYNOTE-010, patients were randomized to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and KEYNOTE-042, patients were randomized to first-line pembrolizumab 200 mg Q3W or platinum-based chemotherapy. Overall survival (OS) was estimated by the Kaplan-Meier method, and safety data were summarized in elderly patients (≥75 years). The analysis included 264 elderly patients with PD-L1-positive tumors (PD-L1 tumor proportion score [TPS] ≥1%); among these, 132 had PD-L1 TPS ≥ 50%. Pembrolizumab improved OS among elderly patients with PD-L1 TPS ≥ 1% (hazard ratio [HR], 0.76 [95% CI, 0.56-1.02]) and PD-L1 TPS ≥ 50% (HR, 0.40 [95% CI, 0.25-0.64]). Pembrolizumab as first-line therapy also improved OS among elderly patients with PD-L1 TPS ≥ 50% (from KEYNOTE-024 and KEYNOTE-042) compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). Pembrolizumab was associated with fewer treatment-related adverse events (AEs) in elderly patients (overall, 68.5% vs 94.3%; grade ≥3, 24.2% vs 61.0%) versus chemotherapy. Immune-mediated AEs and infusion reactions were more common with pembrolizumab versus chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events). In this pooled analysis of elderly patients with advanced NSCLC with PD-L1‒positive tumors, pembrolizumab improved OS versus chemotherapy, with a more favorable safety profile. Outcomes with pembrolizumab in patients ≥75 years were comparable to those in the overall populations in the individual studies.

Nosaki K ，Saka H ，Hosomi Y ，Baas P ，de Castro G Jr ，Reck M ，Wu YL ，Brahmer JR ，Felip E ，Sawada T ，Noguchi K ，Han SR ，Piperdi B ，Kush DA ，Lopes G ... -  《-》

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

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.

Cortellini A ，Cannita K ，Tiseo M ，Cortinovis DL ，Aerts JGJV ，Baldessari C ，Giusti R ，Ferrara MG ，D'Argento E ，Grossi F ，Guida A ，Berardi R ，Morabito A ，Genova C ，Antonuzzo L ，Mazzoni F ，De Toma A ，Signorelli D ，Gelibter A ，Targato G ，Rastelli F ，Chiari R ，Rocco D ，Gori S ，De Tursi M ，Mansueto G ，Zoratto F ，Filetti M ，Bracarda S ，Citarella F ，Russano M ，Cantini L ，Nigro O ，Buti S ，Minuti G ，Landi L ，Ricciardi S ，Migliorino MR ，Natalizio S ，Simona C ，De Filippis M ，Metro G ，Adamo V ，Russo A ，Spinelli GP ，Di Maio M ，Banna GL ，Friedlaender A ，Addeo A ，Pinato DJ ，Ficorella C ，Porzio G ... -  《-》

Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001).

Tamiya M ，Tamiya A ，Hosoya K ，Taniguchi Y ，Yokoyama T ，Fukuda Y ，Hirano K ，Matsumoto H ，Kominami R ，Suzuki H ，Hirashima T ，Uchida J ，Morita M ，Kanazu M ，Sawa N ，Kinoshita Y ，Hara S ，Kumagai T ，Fujimoto D ... -  《-》

Clinical outcomes in non-small cell lung cancer patients with an ultra-high expression of programmed death ligand-1 treated using pembrolizumab as a first-line therapy: A retrospective multicenter cohort study in Japan.

Edahiro R ，Kanazu M ，Kurebe H ，Mori M ，Fujimoto D ，Taniguchi Y ，Suzuki H ，Hirano K ，Yokoyama T ，Morita M ，Fukuda Y ，Uchida J ，Makio T ，Tamiya M ... -  《PLoS One》