1105P - First-line nivolumab plus ipilimumab in advanced melanoma patients previously treated with adjuvant systemic therapy

Background

The combination of nivolumab and ipilimumab (NIVO+IPI) is associated with the most durable responses and the highest overall survival rates in patients (pts) with advanced melanoma. However, this regimen is increasingly being used in a different patient population than in clinical trials, namely after prior adjuvant treatment. The objective of this study is to evaluate the efficacy and safety of NIVO+IPI in pts who have relapsed despite adjuvant treatment.

Methods

This retrospective analysis included pts with unresectable stage III and stage IV melanoma treated with NIVO+IPI between 01/2021-10/2022 at 5 cancer centers in Poland according to uniform criteria. All pts received prior adjuvant therapy (immunotherapy or BRAF/MEK inhibitors) for stage III/IV melanoma.

Results

A total of 70 pts were identified. The median age was 53 years, 32% of pts were female, 46% had BRAF mutation. At baseline, 18.5% of pts had unresectable stage III disease, 21.2% had stage M1a, 18.2% M1b, 34.8% M1c and 7.6% M1d. Most pts (81.4%) received anti-PD1 in the adjuvant setting. In 70% of pts, the disease relapsed during adjuvant therapy. Median follow-up time was 12.6 months. The objective response rate was 24%. A higher response rate was observed in pts who were immunotherapy-naive (33%) than in pts who received anti-PD1 in the adjuvant setting (22%). Median progression-free survival (mPFS) was 3.9 (95%CI 3.0–9.7) months. Although not statistically significant, a higher median PFS of NIVO+IPI was observed in patients who received BRAF/MEK inhibitors as compared to those who were treated with anti-PD1 antibodies in the adjuvant setting (11.1 vs 3.7 months, p=0.53). Overall survival rate at 12 months was 59% (95%Cl 47–74). Treatment-related adverse events (TRAEs) of any grade were observed in 97% of pts and grade 3/4 TRAEs occurred in 24% of pts.

Conclusions

NIVO+IPI shows lower efficacy in advanced melanoma pts who have relapsed despite adjuvant treatment comparing to clinical trial data. The population of pts with a particularly poor prognosis are those previously treated with adjuvant anti-PD-1 antibodies, as disease recurrence indicates some resistance to immunotherapy difficult to overcome by adding anti-CTLA4 antibody to anti-PD-1 therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K. Kozak: Financial Interests, Personal, Invited Speaker: Bristol Myers Squib, MSD, Novartis, Pierre Fabre, Sanofi. P. Teterycz: Financial Interests, Personal, Other: BMS, MSD. L. Galus: Financial Interests, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre. J. Mackiewicz: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, Novartis. B. Cybulska-Stopa, N. Kempa-Kaminska, M. Ziętek, A.M. Czarnecka: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre. P. Sobczuk: Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel Grant: MSD, BMS; Financial Interests, Personal, Invited Speaker: Swixx BioPharma, BMS, Gilead; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Stocks/Shares: CelonPharma; Non-Financial Interests, Institutional, Product Samples: Immutep; Non-Financial Interests, Leadership Role, Board Member, Chair of Young Oncologists Section: Polish Society of Clinical Oncology. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. All other authors have declared no conflicts of interest.