Steven F Powell1, Delvys Rodríguez-Abreu2, Corey J Langer3, Ali Tafreshi4, Luis Paz-Ares5, Hans-Georg Kopp6, Jeronimo Rodríguez-Cid7, Dariusz M Kowalski8, Ying Cheng9, Takayasu Kurata10, Mark M Awad11, Jinaxin Lin12, Bin Zhao12, M Catherine Pietanza12, Bilal Piperdi12, Marina C Garassino13. 1. Sanford Health, Sioux Falls, SD, USA. Electronic address: steven.powell@sanfordhealth.org. 2. Complejo Hospitalario Universitario Insular-Materno Infantil. Universidad de Las Palmas de Gran Canaria, Gran Canaria, Spainospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain. 3. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. 4. Wollongong Private Hospital and University of Wollongong, Wollongong, Australia. 5. Hospital Universitario 12 de Octubre, CNIO, Universidad Complutense and Ciberonc, Madrid, Spain. 6. Robert Bosch Cancer Center, RBCT, Klinik Schillerhöhe, Gerlingen, Germany. 7. Oncology Center, Médica Sur Hospital-Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico. 8. Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 9. Jilin Cancer Hospital, Changchun, Jilin, China. 10. Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Osaka, Japan. 11. Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA. 12. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. 13. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
INTRODUCTION: This exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone. PATIENTS AND METHODS: We pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189/KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for ≥2 weeks (≥4 weeks in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use ≥3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain. RESULTS: 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab plus chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% CI, 0.32‒0.70] and 0.63 [95% CI, 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI, 0.31‒0.62] and 0.55 [95% CI, 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without. CONCLUSION: With or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all PD-L1 subgroups, including patients with PD-L1 tumor proportion score <1%, and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naïve patients with advanced NSCLC, including patients with stable brain metastases.
INTRODUCTION: This exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone. PATIENTS AND METHODS: We pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189/KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for ≥2 weeks (≥4 weeks in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use ≥3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain. RESULTS: 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab plus chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% CI, 0.32‒0.70] and 0.63 [95% CI, 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI, 0.31‒0.62] and 0.55 [95% CI, 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without. CONCLUSION: With or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all PD-L1 subgroups, including patients with PD-L1 tumor proportion score <1%, and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naïve patients with advanced NSCLC, including patients with stable brain metastases.
Authors: Montse Alemany; Marta Domènech; Andreas A Argyriou; Noelia Vilariño; Carles Majós; Pablo Naval-Baudin; Anna Lucas; Ramón Palmero; Marta Simó; Ernest Nadal; Jordi Bruna Journal: Ann Transl Med Date: 2021-04
Authors: Alberto Pavan; Andrea Boscolo Bragadin; Lorenzo Calvetti; Alessandra Ferro; Elisabetta Zulato; Ilaria Attili; Giorgia Nardo; Alessandro Dal Maso; Stefano Frega; Andrea Giovanni Menin; Matteo Fassan; Fiorella Calabrese; Giulia Pasello; Valentina Guarneri; Giuseppe Aprile; PierFranco Conte; Rafael Rosell; Stefano Indraccolo; Laura Bonanno Journal: Transl Lung Cancer Res Date: 2021-01