Masayuki Shirasawa1, Tatsuya Yoshida2, Yuji Matsumoto3, Yuki Shinno4, Yusuke Okuma5, Yasushi Goto6, Hidehito Horinouchi7, Noboru Yamamoto8, Shun-Ichi Watanabe9, Yuichiro Ohe10, Noriko Motoi11. 1. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: mshirasa@ncc.go.jp. 2. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: tatyoshi@ncc.go.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: yumatsum@ncc.go.jp. 4. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: yshinno@ncc.go.jp. 5. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: yokuma@ncc.go.jp. 6. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: ygoto@ncc.go.jp. 7. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: hhorinou@ncc.go.jp. 8. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan; Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: nbryamam@ncc.go.jp. 9. Department of Thoracic Surgery, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: syuwatan@ncc.go.jp. 10. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: yohe@ncc.go.jp. 11. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: nmotoi@ncc.go.jp.
Abstract
BACKGROUND: A history of radiotherapy and chemoradiotherapy (CRT) reportedly increases the efficacy of the PD-1 blockade in patients with advanced non-small cell lung cancer (NSCLC). We investigated the efficacy of anti-PD-(L)1 therapy after CRT failure and how CRT changes the status of PD-L1 expression on tumours and on tumour-infiltrated lymphocytes (TILs). METHODS: We retrospectively reviewed patients with unresectable locally advanced NSCLC (LA-NSCLC) who were treated with CRT between 2007 and 2018 and evaluated the efficacy of the PD-(L)1 blockade after CRT failure. We also compared the PD-L1 (clone: 22C3) expression levels and the tumoral and stromal distributions of CD8-positive TILs using paired formalin-fixed, paraffin-embedded specimens obtained before and after CRT. RESULTS: We identified 422 patients and 65 patients who had relapsed after CRT received anti-PD-(L)1 therapy. The objective response rate (ORR) and the progression-free survival (PFS) after anti-PD-(L)1 therapy were 48% and 8.7 months (95% CI, 4.5-13), respectively. The RR and PFS did not differ according to the pre-CRT PD-L1 expression levels. PD-L1 expression changed in 16 of the 18 patients between before and after CRT, but a specific trend was not seen (increased, 9 patients; decreased, 7 patients; no change, 2 patients). In contrast, the density of tumoral CD8-positive TILs increased after CRT treatment (pre-CRT median, 110/mm2 versus post-CRT median, 470/mm2; p = 0.025). CONCLUSIONS: Anti-PD-(L)1 therapy was effective in patients with LA-NSCLC who had progressed after CRT regardless of their pre-CRT PD-L1 expression. The efficacy of anti-PD-(L)1 therapy for patients with NSCLC with CRT failure was superior to that of standard second-line treatment for patients with advanced NSCLC.
BACKGROUND: A history of radiotherapy and chemoradiotherapy (CRT) reportedly increases the efficacy of the PD-1 blockade in patients with advanced non-small cell lung cancer (NSCLC). We investigated the efficacy of anti-PD-(L)1 therapy after CRT failure and how CRT changes the status of PD-L1 expression on tumours and on tumour-infiltrated lymphocytes (TILs). METHODS: We retrospectively reviewed patients with unresectable locally advanced NSCLC (LA-NSCLC) who were treated with CRT between 2007 and 2018 and evaluated the efficacy of the PD-(L)1 blockade after CRT failure. We also compared the PD-L1 (clone: 22C3) expression levels and the tumoral and stromal distributions of CD8-positive TILs using paired formalin-fixed, paraffin-embedded specimens obtained before and after CRT. RESULTS: We identified 422 patients and 65 patients who had relapsed after CRT received anti-PD-(L)1 therapy. The objective response rate (ORR) and the progression-free survival (PFS) after anti-PD-(L)1 therapy were 48% and 8.7 months (95% CI, 4.5-13), respectively. The RR and PFS did not differ according to the pre-CRT PD-L1 expression levels. PD-L1 expression changed in 16 of the 18 patients between before and after CRT, but a specific trend was not seen (increased, 9 patients; decreased, 7 patients; no change, 2 patients). In contrast, the density of tumoralCD8-positive TILs increased after CRT treatment (pre-CRT median, 110/mm2 versus post-CRT median, 470/mm2; p = 0.025). CONCLUSIONS: Anti-PD-(L)1 therapy was effective in patients with LA-NSCLC who had progressed after CRT regardless of their pre-CRT PD-L1 expression. The efficacy of anti-PD-(L)1 therapy for patients with NSCLC with CRT failure was superior to that of standard second-line treatment for patients with advanced NSCLC.
Authors: Narek Shaverdian; Michael Offin; Annemarie F Shepherd; Charles B Simone; Daphna Y Gelblum; Abraham J Wu; Matthew D Hellmann; Andreas Rimner; Paul K Paik; Jamie E Chaft; Daniel R Gomez Journal: J Thorac Oncol Date: 2021-05-13 Impact factor: 20.121