Long-term survival analysis of TNT: A phase II study of neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma.

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Background: Locally advanced penile squamous cell carcinoma (La-PSCC) is an aggressive malignancy, and the previous standard neoadjuvant TIP regimen has shown moderate efficacy and unfavorable survival outcomes, with an objective response rate (ORR) of 50%, a pathological complete response (pCR) rate of 10%, and median progression-free survival (PFS) and overall survival (OS) of 8.1 months and 17.1 months, respectively. Our preliminary results of the TNT regimen showed promising efficacy, with an ORR of 82.8% and a pCR rate of 48.3%. Here, we present the long-term survival results of this trial with a long time follow-up. Methods: In this multi-center study, single-arm, phase II study, eligible patients with histologically confirmed La-PSCC (cT4/cN3) received TNT regimen (comprising toripalimab, nimotuzumab, and TIP chemotherapy [nab-paclitaxel, cisplatin, and ifosfamide]) every 3 weeks for up to 4 cycles, followed by consolidative surgery. While the primary endpoint was pCR (previously reported), this updated analysis focuses on secondary endpoints, including PFS and OS. The data cutoff date for this analysis was February 10, 2026. Results: With a median follow-up of 59.3 months (range, 2.33-66.93), median PFS and mOS were not reached for the cohort (n=29). The estimated 5-year PFS and OS were 65.5% (95%CI: 50.3%–85.3%) and 69.0% (95%CI: 54.1%–88.2%), respectively. Survival outcomes were significantly stratified by treatment response. In patients achieving a pCR (n=14), the median PFS and OS were not reached. Whereas the non-pCR group (n=15) showed mPFS of 9.7 months (95%CI: 5.63–not reached[NR]) (HR=0.08; 95%CI: 0.009–0.616; p=0.002) and mOS of 33.4 months (95%CI: 12–NR) (HR=0.10; 95%CI: 0.012–0.771; p=0.006). Responders (those achieving a complete response [CR] or partial response [PR], n=24) exhibited significantly better outcomes than non-responders (n=5, all experienced disease progression and death), with median PFS not reached vs 2.47 months (95% CI: 1.7–NR) (HR=0.031, 95%CI: 0.006–0.169, p<0.001) and median OS not reached vs 10.5 months (95% CI, 6.93–NR) (HR=0.033, 95%CI: 0.006–0.181, p<0.001). No new safety signals emerged during the near 5-year follow-up. Conclusions: With a median follow-up of 59.3 months, the TNT regimen continued to provide clinically superior survival outcomes in patients with locally advanced PSCC, maintained by a favorable safety profile. Our findings confirm the long-term durability of TNT regimen, reinforcing its role as a highly effective neoadjuvant strategy for these patients. Clinical trial information: NCT04475016 .