W Yao1, X Zhao2, Y Gong3, M Zhang3, L Zhang2, Q Wu2, L Wu2, Z Fan4, X Yan5, S Jiao6. 1. Medical School of Chinese PLA, Haidian, Beijing, China. 2. Department of Oncology, Chinese PLA General Hospital, Beijing, China. 3. Beijing DCTY® Biotech CO., LTD, Beijing, China. 4. Department of Oncology and Hematology, Shenzhen Third People's Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province, China. 5. Department of Oncology, Chinese PLA General Hospital, Beijing, China. Electronic address: yxiang301@sina.com. 6. Medical School of Chinese PLA, Haidian, Beijing, China. Electronic address: jiaosc301@163.com.
Abstract
BACKGROUND: PD-1/PD-L1 inhibitors in combination with chemotherapy are widely used in clinical practice. However, the ideal combined timing of them has not been fully explored. METHODS: In this study, simulation experiments to explore the impacts of the combination of anti-PD-1 antibody (anti-PD-1 Ab) on the cytotoxic effects of chemotherapeutic drugs in peripheral blood mononuclear cells were performed. In addition, the effects of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on efficacy and safety were retrospectively analysed in patients with refractory lung cancer. RESULTS: Experiments in vitro showed that administering the anti-PD-1 Ab 3 days after chemotherapy (represented by dicycloplatin) resulted in significantly weaker cytotoxic effects on lymphocytes, compared with administering the anti-PD-1 Ab before or concurrent with chemotherapy. Moreover, data from 64 lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy as a second- or higher-line therapy were retrospectively analysed. The results showed that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy was associated with longer overall survival [17.3 months versus 12.7 months; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.28-1.19, P = 0.137 in univariate analysis; HR = 0.36, 95% CI 0.16-0.80, P = 0.012 in multivariate analysis] and a trend of improved progression-free survival (5.1 months versus 4.2 months; HR = 0.81, 95% CI 0.42-1.54, P = 0.512) compared with administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy. CONCLUSION: Our findings suggest that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy is superior to administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy in patients with refractory lung cancer, but this result needs to be further explored by prospective studies.
BACKGROUND:PD-1/PD-L1 inhibitors in combination with chemotherapy are widely used in clinical practice. However, the ideal combined timing of them has not been fully explored. METHODS: In this study, simulation experiments to explore the impacts of the combination of anti-PD-1 antibody (anti-PD-1 Ab) on the cytotoxic effects of chemotherapeutic drugs in peripheral blood mononuclear cells were performed. In addition, the effects of the combined timing of PD-1/PD-L1 inhibitors and chemotherapy on efficacy and safety were retrospectively analysed in patients with refractory lung cancer. RESULTS: Experiments in vitro showed that administering the anti-PD-1 Ab 3 days after chemotherapy (represented by dicycloplatin) resulted in significantly weaker cytotoxic effects on lymphocytes, compared with administering the anti-PD-1 Ab before or concurrent with chemotherapy. Moreover, data from 64 lung cancerpatients treated with PD-1/PD-L1 inhibitors plus chemotherapy as a second- or higher-line therapy were retrospectively analysed. The results showed that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy was associated with longer overall survival [17.3 months versus 12.7 months; hazard ratio (HR) = 0.58, 95% confidence interval (CI) 0.28-1.19, P = 0.137 in univariate analysis; HR = 0.36, 95% CI 0.16-0.80, P = 0.012 in multivariate analysis] and a trend of improved progression-free survival (5.1 months versus 4.2 months; HR = 0.81, 95% CI 0.42-1.54, P = 0.512) compared with administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy. CONCLUSION: Our findings suggest that administering PD-1/PD-L1 inhibitors 1-10 days (especially 3-5 days) after chemotherapy is superior to administering PD-1/PD-L1 inhibitors before or concurrent with chemotherapy in patients with refractory lung cancer, but this result needs to be further explored by prospective studies.
Authors: Andrej Ozaniak; Jitka Smetanova; Robin Bartolini; Michal Rataj; Linda Capkova; Jaromir Hacek; Martina Fialova; Lenka Krupickova; Ilja Striz; Robert Lischke; Jirina Bartunkova; Zuzana Strizova Journal: J Cancer Res Clin Oncol Date: 2022-08-20 Impact factor: 4.322