Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer. (February 2022)

• Record Type: Journal Article
• Authors: Shirasawa, Masayuki; Yoshida, Tatsuya; Imabayashi, Tatsuya; Okuma, Kae; Matsumoto, Yuji; Masuda, Ken; Shinno, Yuki; Okuma, Yusuke; Goto, Yasushi; Horinouchi, Hidehito; Tsuchida, Takaaki; Yamamoto, Noboru; Nakayama, Yuko; Watanabe, Shun-ichi; Motoi, Noriko; Ohe, Yuichiro
• Is Part Of: European journal of cancer. Volume 162(2022)
• Page Start: 1
• Page End: 10
• Publication Date: 2022-02
• Subjects: Locally advanced non-small-cell carcinoma -- Durvalumab -- Tumour-infiltrated lymphocytes -- and PD-L1 expression -- CD8; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.11.013
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Chemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of the immune-related tumour microenvironment (TME) at baseline associates with the efficacy. Methods: This retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group). Results: A total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached [NR] vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm 2 ) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77). Conclusions: PD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab. Highlights: In unresectable locally advanced-non-small-cell lung cancer (LA-NSCLC), it is unclear what patients can benefit from durvalumab. The progression-free survival (PFS) of chemoradiation (CRT) alone did not differ as per PD-L1 expression and tumour-infiltrating lymphocytes (TIL) status. PD-L1 expression and TIL status predicted longer PFS of CRT followed by durvalumab. PD-L1 expression was significantly associated with TIL status in LA-NSCLC.