BACKGROUND: Long-term responders have been observed with anti-programmed death 1 and anti-programmed death ligand 1 (anti-PD(L)1). Optimal duration of therapy in responding and stable disease (SD) patients is unclear with various attitudes encompassing treatment until progression disease, stopping therapy after a defined timeframe. PATIENTS AND METHODS: We report the experience of 13 patients who discontinued immune checkpoint inhibitor in phase I trials as per protocol while experiencing a tumour-controlled disease. According to protocols, patients could restart the same immunotherapy if radiological or clinical progression occurred. RESULTS: Patients were treated for colorectal microsatellite instability-high genotype (n = 5), urothelial carcinoma (n = 3), melanoma (n = 2), non-small-cell lung cancer (n = 2) and triple-negative breast cancer (n = 1) for a median time of 12 months (range 10.6-12). Patients achieved 1 (8%) complete response, 10 (77%) partial response (PR) and 2 (15%) SD. The median progression-free survival 1 (PFS1) defined as the time from the first infusion until progression was 24.4 months (range 15.8-49). The median time free-treatment after discontinuation was 12.6 months (range 4-39.7). Eight patients experienced disease progression and were retreated. Best responses observed after rechallenging were 2 PR (25%) and 6 SD (75%). Median PFS2 defined from the first day of retreatment until disease progression or the last news was 12.9 months (range 5-35.4). No grade 3/4 events occurred during the study period. CONCLUSION: Our data suggest that anti-PD(L)1 therapy should be resumed if progression occurs after a planned anti-PD(L)1 interruption. Further prospective studies are needed to confirm these results.
BACKGROUND: Long-term responders have been observed with anti-programmed death 1 and anti-programmed death ligand 1 (anti-PD(L)1). Optimal duration of therapy in responding and stable disease (SD) patients is unclear with various attitudes encompassing treatment until progression disease, stopping therapy after a defined timeframe. PATIENTS AND METHODS: We report the experience of 13 patients who discontinued immune checkpoint inhibitor in phase I trials as per protocol while experiencing a tumour-controlled disease. According to protocols, patients could restart the same immunotherapy if radiological or clinical progression occurred. RESULTS:Patients were treated for colorectal microsatellite instability-high genotype (n = 5), urothelial carcinoma (n = 3), melanoma (n = 2), non-small-cell lung cancer (n = 2) and triple-negative breast cancer (n = 1) for a median time of 12 months (range 10.6-12). Patients achieved 1 (8%) complete response, 10 (77%) partial response (PR) and 2 (15%) SD. The median progression-free survival 1 (PFS1) defined as the time from the first infusion until progression was 24.4 months (range 15.8-49). The median time free-treatment after discontinuation was 12.6 months (range 4-39.7). Eight patients experienced disease progression and were retreated. Best responses observed after rechallenging were 2 PR (25%) and 6 SD (75%). Median PFS2 defined from the first day of retreatment until disease progression or the last news was 12.9 months (range 5-35.4). No grade 3/4 events occurred during the study period. CONCLUSION: Our data suggest that anti-PD(L)1 therapy should be resumed if progression occurs after a planned anti-PD(L)1 interruption. Further prospective studies are needed to confirm these results.
Authors: Vaia Florou; Christopher Nevala-Plagemann; Kristin E Barber; Jenna N Mastroianni; Courtney C Cavalieri; Ignacio Garrido-Laguna Journal: JCO Precis Oncol Date: 2020-06-30
Authors: Rachel Rosenthal; Elizabeth Larose Cadieux; Roberto Salgado; Maise Al Bakir; David A Moore; Crispin T Hiley; Tom Lund; Miljana Tanić; James L Reading; Kroopa Joshi; Jake Y Henry; Ehsan Ghorani; Gareth A Wilson; Nicolai J Birkbak; Mariam Jamal-Hanjani; Selvaraju Veeriah; Zoltan Szallasi; Sherene Loi; Matthew D Hellmann; Andrew Feber; Benny Chain; Javier Herrero; Sergio A Quezada; Jonas Demeulemeester; Peter Van Loo; Stephan Beck; Nicholas McGranahan; Charles Swanton Journal: Nature Date: 2019-03-20 Impact factor: 49.962