Adjuvant chemotherapy based on the intratumoral expressions of class III beta tubulin and thymidylate synthase improved disease-free survival in patients with resected locally advanced non-small cell lung cancer

Objectives: Although the molecular targeted therapy and immune-check point inhibitors improved survival of some populations of patients with non-small cell lung cancer (NSCLC), most of patients still remain to need conventional chemotherapy. Adjuvant chemotherapy is recommended for patients with resected locally advanced NSCLC. However, selection of the optimal adjuvant chemotherapy regimen is difficult. Regarding the predictive biomarkers for chemotherapy, the intratumoral expressions of class III β tubulin (TUBB3) has been reported to be a biomarker for taxanes, and thymidylate synthase (TS) for 5-fluorouracil (5-FU) derivatives and pemetrexed. Therefore, we conducted a prospective clinical study to evaluate the effectiveness of tailor-made adjuvant chemotherapy based on TUBB3 and TS. Methods: Between November 2011 and December 2016, 54 patients with pathological stage IIB to IIIB NSCLC who underwent complete resection were studied. The expressions of TUBB3 and TS were estimated by immunohistochemistry. When less than 50% of the tumor cells in a given specimen were positively stained for TUBB3, the tumor was classified as TUBB3-low. When less than 50% of the tumor cells in a given specimen were positively stained for TS, the tumor was classified as TS-low. Concerning to adjuvant chemotherapy, patients with TUBB3-low tumors were preferably treated with Taxane-based chemotherapy, and patients with TS-low tumors were preferably treated with chemotherapy including 5-FU derivatives or pemetrexed. Patients who could receive tailor-made adjuvant chemotherapy based on evaluations of TUBB3 and TS were assigned to tailor-made group. Patients who could not receive tailor-made adjuvant chemotherapy were assigned to non-tailor-made group, due to several reasons, such as both TUBB3-high and TS-high tumors and renal dysfunction. Results: Among 54 tumors, 39 tumors were adenocarcinomas, 14 were squamous cell carcinomas, and 1 was adenosquamous cell carcinoma. Regarding pathological stage, 19 tumors were stage IIB, 32 were stage IIIA, and 3 were stage IIIB. Concerning to survival, the disease-free survival (DFS) rate was significantly higher in tailor-made group than in non-tailor-made group (5-year DFS rate: 58.6% vs 12.0%; P Conclusion: Adjuvant chemotherapy based on the intratumoral expressions of TUBB3 and TS is considered to be clinically useful for patients with resected locally advanced NSCLC. Citation Format: Ryota Sumitomo, Tatsuya Hirai, Hiyoaki Murakami, Yosuke Otake, Cheng-long Huang. Adjuvant chemotherapy based on the intratumoral expressions of class III β tubulin and thymidylate synthase improved disease-free survival in patients with resected locally advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4010.