Open AccessPresence of few PD‐1‐expressing tumor‐infiltrating immune cells is a potential predictor of improved response to salvage chemotherapy following nivolumab for non‐small cell lung cancer: An exploratory case series
Author(s) -
Ogawara Daiki,
Soda Hiroshi,
Tomono Hiromi,
Iwasaki Keisuke,
Hara Takuya,
Jinnai Saeko,
Funayama Takatomo,
Okuno Daisuke,
Taniguchi Hirokazu,
Yoshida Masataka,
Harada Tatsuhiko,
Umemura Asuka,
Fukuda Yuichi,
Yamaguchi Hiroyuki,
Mukae Hiroshi
Publication year - 2018
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12844
Subject(s) - nivolumab , medicine , lung cancer , chemotherapy , immune system , oncology , pd l1 , cancer research , programmed cell death 1 , immunotherapy , immunology
Background The combination of PD‐1 inhibitors and cytotoxic drugs is reported to enhance anti‐tumor activity in non‐small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor‐infiltrating immune cells. Methods The medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression‐free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab. Results Eight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4–90.6%; P = 0.004) and median progression‐free survival to six months (95% CI 4.6–7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD‐L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm 2 of PD‐1 + immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm 2 . Responders had fewer PD‐1 + immune cells than non‐responders (percentage P = 0.028; density P = 0.034). Conclusion Salvage chemotherapy following nivolumab improved anti‐tumor activity regardless of tumor PD‐L1 status, but nivolumab following chemotherapy did not. The presence of few PD‐1 + tumor‐infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re‐sensitizes the tumor immune microenvironment to chemotherapy.