PURPOSE: Prior data suggest driver-mutated NSCLC, especially EGFR and ALK tumors, poorly respond to immunotherapy. However, little research using real-world cohorts have been performed, nor is it clear whether PD-L1 and smoking history are predictive of outcomes in such tumors. This study assessed rwPFS in a large cohort with driver-mutated advanced NSCLC treated with single-agent PD-1/PDL-1 inhibitors. METHODS: Real-world data from 1746 patients were analyzed and rwPFS with immunotherapy was determined for EGFR, ALK, BRAF, and KRAS tumors. Kaplan-Meier curves characterized rwPFS and correlated with PD-L1 and smoking history. Comparisons were tested using log-rank. RESULTS: Median rwPFS and the percent progression-free at 12 months were greater among KRAS (3.3 months, 21.1%) and BRAF (3.6 months, 20.6%) as compared to EGFR (2.5 months, 8.1%) and ALK tumors (2.3 months, 11.2%). KRAS tumors with PD-L1 ≥ 1% had longer rwPFS than PD-L1 < 1% tumors (4.1 versus 3.2 months, p = 0.001). PD-L1 positivity did not predict rwPFS in EGFR, ALK, or BRAF tumors. However, a smoking history was associated with longer rwPFS in EGFR (2.6 versus 2.3 months, p = 0.048) and ALK tumors (3.0 versus 2.1 months, p = 0.049) as compared to no smoking history. CONCLUSION: Real-world PFS with immunotherapy was greater in KRAS and BRAF as compared to EGFR and ALK tumors. PD-L1 positivity was predictive in KRAS and not associated with rwPFS in other mutation types. While median rwPFS was short for EGFR and ALK tumors, small subsets were progression-free at 12 months. Better characterizing these subsets that benefit, along with developing strategies to overcome immunotherapy resistance in EGFR/ALK tumors are needed.
PURPOSE: Prior data suggest driver-mutated NSCLC, especially EGFR and ALK tumors, poorly respond to immunotherapy. However, little research using real-world cohorts have been performed, nor is it clear whether PD-L1 and smoking history are predictive of outcomes in such tumors. This study assessed rwPFS in a large cohort with driver-mutated advanced NSCLC treated with single-agent PD-1/PDL-1 inhibitors. METHODS: Real-world data from 1746 patients were analyzed and rwPFS with immunotherapy was determined for EGFR, ALK, BRAF, and KRAS tumors. Kaplan-Meier curves characterized rwPFS and correlated with PD-L1 and smoking history. Comparisons were tested using log-rank. RESULTS: Median rwPFS and the percent progression-free at 12 months were greater among KRAS (3.3 months, 21.1%) and BRAF (3.6 months, 20.6%) as compared to EGFR (2.5 months, 8.1%) and ALK tumors (2.3 months, 11.2%). KRAS tumors with PD-L1 ≥ 1% had longer rwPFS than PD-L1 < 1% tumors (4.1 versus 3.2 months, p = 0.001). PD-L1 positivity did not predict rwPFS in EGFR, ALK, or BRAF tumors. However, a smoking history was associated with longer rwPFS in EGFR (2.6 versus 2.3 months, p = 0.048) and ALK tumors (3.0 versus 2.1 months, p = 0.049) as compared to no smoking history. CONCLUSION: Real-world PFS with immunotherapy was greater in KRAS and BRAF as compared to EGFR and ALK tumors. PD-L1 positivity was predictive in KRAS and not associated with rwPFS in other mutation types. While median rwPFS was short for EGFR and ALK tumors, small subsets were progression-free at 12 months. Better characterizing these subsets that benefit, along with developing strategies to overcome immunotherapy resistance in EGFR/ALK tumors are needed.
Authors: Leena Gandhi; Delvys Rodríguez-Abreu; Shirish Gadgeel; Emilio Esteban; Enriqueta Felip; Flávia De Angelis; Manuel Domine; Philip Clingan; Maximilian J Hochmair; Steven F Powell; Susanna Y-S Cheng; Helge G Bischoff; Nir Peled; Francesco Grossi; Ross R Jennens; Martin Reck; Rina Hui; Edward B Garon; Michael Boyer; Belén Rubio-Viqueira; Silvia Novello; Takayasu Kurata; Jhanelle E Gray; John Vida; Ziwen Wei; Jing Yang; Harry Raftopoulos; M Catherine Pietanza; Marina C Garassino Journal: N Engl J Med Date: 2018-04-16 Impact factor: 91.245
Authors: Hossein Borghaei; Luis Paz-Ares; Leora Horn; David R Spigel; Martin Steins; Neal E Ready; Laura Q Chow; Everett E Vokes; Enriqueta Felip; Esther Holgado; Fabrice Barlesi; Martin Kohlhäufl; Oscar Arrieta; Marco Angelo Burgio; Jérôme Fayette; Hervé Lena; Elena Poddubskaya; David E Gerber; Scott N Gettinger; Charles M Rudin; Naiyer Rizvi; Lucio Crinò; George R Blumenschein; Scott J Antonia; Cécile Dorange; Christopher T Harbison; Friedrich Graf Finckenstein; Julie R Brahmer Journal: N Engl J Med Date: 2015-09-27 Impact factor: 91.245
Authors: Justin F Gainor; Alice T Shaw; Lecia V Sequist; Xiujun Fu; Christopher G Azzoli; Zofia Piotrowska; Tiffany G Huynh; Ling Zhao; Linnea Fulton; Katherine R Schultz; Emily Howe; Anna F Farago; Ryan J Sullivan; James R Stone; Subba Digumarthy; Teresa Moran; Aaron N Hata; Yukako Yagi; Beow Y Yeap; Jeffrey A Engelman; Mari Mino-Kenudson Journal: Clin Cancer Res Date: 2016-05-25 Impact factor: 12.531
Authors: Erica K Barnell; Adam Waalkes; Matt C Mosior; Kelsi Penewit; Kelsy C Cotto; Arpad M Danos; Lana M Sheta; Katie M Campbell; Kilannin Krysiak; Damian Rieke; Nicholas C Spies; Zachary L Skidmore; Colin C Pritchard; Todd A Fehniger; Ravindra Uppaluri; Ramaswamy Govindan; Malachi Griffith; Stephen J Salipante; Obi L Griffith Journal: JCO Clin Cancer Inform Date: 2019-10