1332 - Combined ipilimumab and nivolumab first-line and after BRAF-directed targeted therapies in advanced melanoma patients

Background

Combination ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. How best to integrate this combination into clinical practice, in real-world patients, and in the setting of BRAF targeted therapy, is not clear. We sought to explore the safety and efficacy of combination ipilimumab and nivolumab in such a population.

Methods

Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab via an early access scheme across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, prior and subsequent systemic treatments, toxicity, RECIST response and survival outcomes.

Results

152 patients were included for analysis, including 60 (39%) treatment-naïve and 33 (22%) who had failed first-line BRAF/MEK inhibitors and then treated with combination therapy second-line. In the whole cohort, most patients had a high AJCC M stage (63% M1c, 26% M1d) and elevated LDH (55%), with similar distribution of adverse features in the treatment naïve and BRAF/MEK failure subgroups. Treatment-related adverse events occurred in 102 (67%) patients, grade 3-5 in 38% (1 death from immune myocarditis). The objective response rate was 41% in the whole cohort, 57% (17% complete) in treatment naïve, and only 21% (3% complete) in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0 to 6.0) in the whole cohort, 11.0 months (95% CI, 6.0 - NR) in treatment-naïve patients, and 2.0 months (95% CI, 1.4 - 4.6) in BRAF/MEK failure patients.

Conclusions

Combination ipilumumab and nivolumab can be used safely and effectively in a real-world population, including in patients that are heavily pre-treated and those with adverse disease characteristics. While first-line efficacy appears comparable to that seen in trial populations, BRAF-mutant patients who have failed prior BRAF/MEK inhibitors are less likely to respond, supporting first-line use of combination immunotherapy in the majority of newly diagnosed poor prognosis metastatic melanoma patients.

Clinical trial identification

Legal entity responsible for the study

A. Menzies.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

H.C. Dearden: Travel expenses support: MSD. R. Mason: Travel expenses support: Bristol-Myers Squibb. J.A. Soon: Travel expenses support: Pfizer. M. Randhawa: Travel expenses support: Merck. A. Mant: Consultancy: Novartis. L. Warburton: Travel expenses support: MSD. T. Meniawy: Honoraria; Consultancy: AstraZeneca/MedImmune; Research funding: Incyte, BeiGene, AstraZeneca/MedImmune, Regeneron, Bayer, Roche/Genetech, Bristol Myers Squibbs, Merck Serono Ltd; Travel expenses support: Roche/Genetech. A. Guminski: Consultancy for Roche, Regeneron, Eisai, Sun Pharma, Bristol Myers Squibbs; Travel and expenses support: Sun Pharma, Bristol Myers Squibb. S. Ali: Honoraria and consultancy: Bristol Myers Squibb. G.V. Long: Consultancy: Bristol-Myers Squibb, Roche/Genentech, Amgen, Merck, Novartis, Array BioPharma, Pierre Fabre, Incycte; Honoraria: Bristol-Myers Squibb, Merck, Roche, Novartis, Incycte. M.S. Carlino: Consultancy: Bristol-Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre; Honoraria: Bristol-Myers Squibb, MSD, Novartis. M. Millward: Consultancy: AstraZeneca, MSD, Roche, Bristol Myers Squibbs; Travel expenses support: Roche, MSD, Bristol Myers Squibb. V.G. Atkinson: Honoraria; Novartis, Bristol Myers Squibbs; Consultancy: Novartis, Pierre Fabre, Bristol Myers Squibbs, Merck Serono Ltd, MSD; Travel expenses support: Bristol Myers Squibb. A.M. Menzies: Consultancy: MSD, Novartis, Pierre Fabre, Bristol-Myers Squibb, Roche; Travel expenses support: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.