Improved 5-year survival outcomes reported for resectable NSCLC patients treated with neoadjuvant nivolumab

A recent study by Patrick Forde and Samuel Rosner (both Sidney Kimmel Comprehensive Cancer Center at John Hopkins; MD, USA) followed the 5-year clinical outcomes of 20 Stage I−III resectable NSCLC patients receiving neoadjuvant Opdivo™ (nivolumab), with a focus on recurrence-free and overall survival rates. The study was funded by multiple companies and institutions. It is a follow-on from their previous research that reported a Phase I/II clinical trial analyzing the efficacy and safety of patients treated with two doses of neoadjuvant nivolumab.

Of the 20 patients enrolled in the study, 45% of patients were independent of tumor PD-L1 expression and when looking at major pathological responses, 73% were recurrence-free after the tumors were surgically resected 18 months subsequently.

Senior author of the study Forde stated: “To our knowledge, this is the longest follow-up to date for a PD-1/PD-L1 inhibitor in the neoadjuvant setting for any solid tumor.”

In the final analysis of the 20 patients, 60% remained recurrence-free and the overall survival rate was 80% which co-first author Rosner noted exceeded the average 36−68% that has been observed in previous studies.

In addition, nine of the 20 patients had a major pathological response after neoadjuvant nivolumab treatment and were identified to have a potential biomarker for recurrence-free and overall survival. Eight of the nine patients were cancer-free following the 5-year clinical outcomes of neoadjuvant nivolumab, with the remaining patient having passed away from non-cancer related complications. Of the eight surviving patients, one experienced recurrence less than a year after the treatment, however received further definitive chemoradiation and has been disease-free since.

The remaining 11 patients who did not experience a major pathological response did have some form of recurrence, with a total of three cancer-related deaths. Rosner commented: “An interesting finding from the analysis was the difference in outcomes between patients with and without a major pathological response.”

Overall, the results could mean that a neoadjuvant nivolumab major pathological response may have an association with a lower risk of disease recurrence and death.  While the study has shown promising results and hope for the future, the limitations of a single-arm design and relatively small cohort size should be noted. The authors caution that these results are preliminary and should be carried out in further studies with large cohort groups. However, despite the limitations, Forde concluded that: “the long-term safety and efficacy data from this study provide further support for the use of nivolumab in the neoadjuvant setting.”

Sources: Rosner S, Reuss EJ, Zahurak M et al. Five-year clinical outcomes after neoadjuvant nivolumab in resectable non–small cell lung cancer. Clin. Cancer Res. 29(4), 705−710 doi:10.1158/1078-0432.CCR-22-2994 (2023); www.aacr.org/about-the-aacr/newsroom/news-releases/neoadjuvant-nivolumab-shows-long-term-benefit-in-patients-with-non-small-cell-lung-cancer/