Nivolumab/Ipilimumab Improves Real-World Melanoma Outcomes Vs Pembrolizumab

"The use of combination immunotherapy regimens (nivolumab [plus] ipilimumab) is associated with higher rates of pathological response and a trend toward improved PFS compared to monotherapy (pembrolizumab)," according to the study authors.

Neoadjuvant treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) appeared to improve pathological responses and trended towards longer progression-free survival (PFS) vs pembrolizumab (Keytruda) monotherapy in patients with stage III/IV cutaneous melanoma, according to real-world findings from a poster presentation at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting.1

Among patients who received nivolumab plus ipilimumab, the major pathological response (MPR) rate was 71.4% vs 32.2% in those who received pembrolizumab alone (P = .01). Data also revealed a pathologic complete response (pCR) rate of 42.6% vs 29.0% in each population. Additionally, the radiological objective response rate (ORR) was 57.1% and 51.6% in each group (P = .78).

In the nivolumab/ipilimumab and pembrolizumab groups, the PFS rates were 87% vs 77% at 1 year and 87% vs 68% at 2 years (P = .171). The 2-year PFS rates were 94% in patients who achieved MPRs vs 61% in those who did not; MPRs correlated with significantly improved PFS (P = .026).

“The use of neoadjuvant/perioperative immunotherapy in the NADINA [NCT04949113] and SWOG S1801 trials [NCT03698019] has shown improved treatment outcomes in stage III cutaneous melanoma compared to adjuvant therapy. However, real-world data on neoadjuvant immunotherapy remain limited,” Alexandr Iurchenkov, MD, from Moscow City Oncology Hospital #62 in Moscow, Russia, wrote with coauthors in the poster.1-3 “The use of combination immunotherapy regimens (nivolumab [plus] ipilimumab) is associated with higher rates of pathological response and a trend toward improved PFS compared to monotherapy (pembrolizumab).”

Investigators retrospectively evaluated 52 patients who received neoadjuvant immunotherapy at a single academic center for resectable stage III or IV cutaneous melanoma. Patients received either nivolumab in combination with ipilimumab (n = 21) or pembrolizumab alone (n = 31). Those who achieved an MPR during combination therapy did not receive additional adjuvant therapy; patients in the pembrolizumab group continued adjuvant treatment for a maximum of 1 year.

Radiological responses were evaluated per RECIST v1.1 guidelines. Additionally, investigators assessed patients for MPRs and pCRs while estimating survival outcomes based on Kaplan-Meier analysis.

The median patient age was 65 years (range, 30-90), and most patients were female (47.5%). Most patients had no BRAF mutations (67.2%) and a lower lactate dehydrogenase level (82%).

Investigators administered 2 planned cycles of neoadjuvant nivolumab/ipilimumab to 20 of 21 patients in the combination therapy group. One patient did not undergo the second cycle of therapy due to immune-mediated hepatitis. Additionally, patients received pembrolizumab monotherapy for a median of 3 cycles (range, 2-8). All patients in the combination therapy group underwent surgery compared with 28 of 31 patients who received pembrolizumab monotherapy. In the pembrolizumab group, 2 patients did not undergo surgery due to disease progression, and 1 refused to proceed with surgery.

Adverse effects of higher than grade 2 occurred in 19.0% of patients who received nivolumab/ipilimumab compared with 12.9% who received pembrolizumab monotherapy.

Previously published data from the phase 3 NADINA trial showed that neoadjuvant nivolumab plus ipilimumab followed by surgery and response-based adjuvant therapy improved event-free survival (EFS) vs surgery plus adjuvant nivolumab alone in patients with stage III melanoma (HR, 0.32; 95% CI, 0.15-0.66; P <.001).2 Furthermore, in the phase 2 SWOG S1801 trial, investigators noted that EFS significantly improved with perioperative pembrolizumab plus surgery compared with adjuvant pembrolizumab and surgery among those with resectable stage III or IV melanoma (P = .004).3

References

1. Iurchenkov A, Stroyakovskiy D, Danilova A, et al. Real-world effectiveness of neoadjuvant immunotherapy in resectable stage III–IV melanoma: a comparative analysis of nivolumab/ipilimumab versus pembrolizumab. Presented at the Society for Immunotherapy of Cancer (SITC) 2025 Annual Meeting, National Harbor, MD; November 5-9, 2025. Abstract 525.
2. Blank CU, Lucas MW, Scolyer RA, et al. Neoadjuvant nivolumab and ipilimumab in resectable stage III melanoma. N Engl J Med. 2024;391(18):1696-1708. doi: 10.1056/NEJMoa2402604.
3. Patel SP, Othus M, Chen Y, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med. 2023;388(9):813-823. doi:10.1056/NEJMoa2211437.