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

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 ex-pression was measured were included in the study. This was a retrospective study conducted using electronic medi-cal 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 can-cer 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