Effect of the thyroid transcription factor 1 expression and treatment discontinuation due to adverse events on progression-free survival in patients with advanced non-squamous non-small cell lung cancer treated with pembrolizumab plus pemetrexed and platinum chemotherapy: a Japanese four-hospital, retrospective study

甲状腺转录因子1表达及因不良事件导致的治疗中断对接受帕博利珠单抗联合培美曲塞和铂类化疗的晚期非鳞状非小细胞肺癌患者无进展生存期的影响:一项日本四家医院的回顾性研究

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Abstract

Although a significant improvement in progression-free survival (PFS) has been reported in the thyroid transcription factor 1 (TTF-1) positive patients under treatment for non-squamous non-small cell lung cancer (NS-NSCLC), including immune checkpoint inhibitor therapy, the association between TTF-1 expression and adverse event occurrence remains unclear. Therefore, this study investigated the impact of TTF-1 and its adverse events on PFS during pembrolizumab plus pemetrexed and platinum chemotherapy for NS-NSCLC. Patients who received the pembrolizumab plus pemetrexed and platinum chemotherapy from 1/1/2018 to 12/31/2022 and whose TTF-1 expression was measured were included in the study. This was a retrospective study conducted using electronic medical records. The mean age of the 79 patients was 67.5 ± 8.4 years, with 75.95% patients being male. Among them, 59.49% were TTF-1 positive. PFS comparison between TTF-1-positive and -negative patients showed a trend toward longer PFS for TTF-1 positive patients, though the results were statistically insignificant (P = 0.190). Proportional hazards analysis indicated significant PFS extension from treatment interruption, as adverse events related to cancer therapy stopped (hazard ratio [HR] = 0.32, P = 0.005) and the number of anticancer agents used (HR = 0.01, P < 0.001). Additionally, pembrolizumab plus pemetrexed and platinum chemotherapy for TTF-1-positive NS-NSCLC significantly extended PFS after treatment discontinuation as related adverse events stopped (827 vs. 210 days, P = 0.021). Measurement of TTF-1 may accordingly serve as a predictor of treatment response to the pembrolizumab plus pemetrexed and platinum chemotherapy. It may also be a predictor of patient prognosis when treatment is discontinued due to related adverse events.

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