J Cancer 2020; 11(3):741-749. doi:10.7150/jca.37966

Research Paper

Anti-PD-1 Therapy plus Chemotherapy and/or Bevacizumab as Second Line or later Treatment for Patients with Advanced Non-Small Cell Lung Cancer

Fan Zhang1*, Di Huang2,1*, Tao Li1*, Sujie Zhang1, Jinliang Wang1, Yuzi Zhang3, Guoqiang Wang3, Zhengyi Zhao3, Junxun Ma1, Lijie Wang1, Danyang Sun1, Pengfei Cui1, Shangli Cai3, Shunchang Jiao1, Lei Zhao4✉, Yi Hu1,2✉

1. Department of Oncology, Chinese PLA General Hospital, PLA School of Medicine, Beijing, People's Republic of China
2. School of medicine, Nankai University, Tianjin, People's Republic of China
3. The Medical Department, 3D Medicines Inc., Shanghai, People's Republic of China
4. National Clinical Research Center for Normal Aging and Geriatric & The Key Lab of Normal Aging and Geriatric, Institute of Geriatric, PLA General Hospital, Beijing, People's Republic of China
*Three authors contributed equally to this work.

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Zhang F, Huang D, Li T, Zhang S, Wang J, Zhang Y, Wang G, Zhao Z, Ma J, Wang L, Sun D, Cui P, Cai S, Jiao S, Zhao L, Hu Y. Anti-PD-1 Therapy plus Chemotherapy and/or Bevacizumab as Second Line or later Treatment for Patients with Advanced Non-Small Cell Lung Cancer. J Cancer 2020; 11(3):741-749. doi:10.7150/jca.37966. Available from http://www.jcancer.org/v11p0741.htm

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Immune checkpoint inhibitor combination therapy exhibited outstanding efficacy in first line setting for advanced non-small cell lung cancer (aNSCLC) patients. However, whether PD-1 inhibitor combined treatment is effective in second line or later setting remains unknown. Therefore, we retrospectively evaluated the efficacy of combined therapy of PD-1 inhibitor with chemotherapy and/or bevacizumab compared to PD-1 inhibitor alone for aNSCLC patients in second line or later setting. Patients with aNSCLC who have received anti-PD-1 based therapy between 2015 and 2017 were screened, and 55 patients were ultimately included and divided into the monotherapy group (N=33) and the combination group (N=22). Patients treated with combination therapy exhibited superior PFS versus those treated with monotherapy (median PFS, 7.5 months vs 3.3 months; hazard ratio 0.28; 95% CI, 0.14-0.56; P<0.001). Objective response rate and disease control rate were 31.8% (7/22) and 95.5% (21/22) in the combination group and 10.0% (3/30) and 46.7% (14/30) in the monotherapy group, respectively (ORR, P=0.075; DCR, P<0.001). Five patients (22.7%) experienced grade 3-4 adverse events in the combination group and two patients (6.1%) in the monotherapy group. Taken together, our results indicated that for NSCLC patients who had failed on the first-line or later treatment, PD-1 inhibitor in combination with chemotherapy and/or bevacizumab might be a favorable treatment option. These findings warrant further validation in prospective studies.

Keywords: immune checkpoint inhibitor, combination therapy, non-small cell lung cancer