Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study
Kazutaka Hosoya,
Daichi Fujimoto,
Takeshi Morimoto,
Toru Kumagai,
Akihiro Tamiya,
Yoshihiko Taniguchi,
Toshihide Yokoyama,
Tadashi Ishida,
Hirotaka Matsumoto,
Katsuya Hirano,
Ryota Kominami,
Keisuke Tomii,
Hidekazu Suzuki,
Tomonori Hirashima,
Satoshi Tanaka,
Junji Uchida,
Mitsunori Morita,
Masaki Kanazu,
Masahide Mori,
Kenji Nagata,
Ikue Fukuda,
Motohiro Tamiya
Affiliations
Kazutaka Hosoya
Department of Respiratory Medicine, Kobe City Medical Center General Hospital
Daichi Fujimoto
Department of Respiratory Medicine, Kobe City Medical Center General Hospital
Takeshi Morimoto
Clinical Research Center, Kobe City Medical Center General Hospital
Toru Kumagai
Department of Thoracic Oncology, Osaka International Cancer Institute
Akihiro Tamiya
Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center
Yoshihiko Taniguchi
Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center
Toshihide Yokoyama
Department of Respiratory Medicine, Kurashiki Central Hospital
Tadashi Ishida
Department of Respiratory Medicine, Kurashiki Central Hospital
Hirotaka Matsumoto
Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center
Katsuya Hirano
Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center
Ryota Kominami
Department of Respiratory Medicine, Himeji Medical Center
Keisuke Tomii
Department of Respiratory Medicine, Kobe City Medical Center General Hospital
Hidekazu Suzuki
Department of Thoracic Oncology, Osaka Habikino Medical Center
Tomonori Hirashima
Department of Thoracic Oncology, Osaka Habikino Medical Center
Satoshi Tanaka
Department of Respiratory Medicine, Osaka General Medical Center
Junji Uchida
Department of Respiratory Medicine, Osaka General Medical Center
Mitsunori Morita
Department of Respiratory Medicine, Kobe City Medical Center West Hospital
Masaki Kanazu
Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center
Masahide Mori
Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center
Kenji Nagata
Department of Respiratory Medicine, Itami City Hospital
Ikue Fukuda
Department of Respiratory Medicine, Itami City Hospital
Motohiro Tamiya
Department of Thoracic Oncology, Osaka International Cancer Institute
Abstract Background Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. Methods We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. Results Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. Conclusions Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
