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. 2024 Oct 4;16(19):3397.
doi: 10.3390/cancers16193397.

Survival of Patients with Metastatic Melanoma Treated with Ipilimumab after PD-1 Inhibitors: A Single-Center Real-World Study

Sofia Verkhovskaia  1 , Rosa Falcone  1 , Francesca Romana Di Pietro  1 , Maria Luigia Carbone  2 , Tonia Samela  3 , Marie Perez  4 , Giulia Poti  1 , Maria Francesca Morelli  1 , Albina Rita Zappalà  1 , Zorika Christiana Di Rocco  1 , Roberto Morese  1 , Gabriele Piesco  1 , Paolo Chesi  1 , Paolo Marchetti  1 , Damiano Abeni  3 , Cristina Maria Failla  5 , Federica De Galitiis  1
Affiliations

Survival of Patients with Metastatic Melanoma Treated with Ipilimumab after PD-1 Inhibitors: A Single-Center Real-World Study

Sofia Verkhovskaia et al. Cancers (Basel). .

Abstract

Background: When monotherapy with PD-1 inhibitors in metastatic melanoma fails, there are currently no standard second-line choices. In case of the unavailability of clinical trials, ipilimumab represents a possible alternative treatment.

Methods: We collected data of 44 patients who received ipilimumab after the failure of PD-1 inhibitors from July 2017 to May 2023 at our Institute. Overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) based on BRAF or NRAS mutation status, sex, and the presence of brain metastases were estimated using the Kaplan-Meier method. Cox regression was used to evaluate independence in multivariate analysis. The objective response rate (ORR) was estimated based on RECIST 1.1.

Results: Among the 44 patients enrolled in this study, 28 BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated patients were identified. OS analysis showed a significant difference between wildtype and BRAF- or NRAS-mutated patients: 23.2 months vs 5.3 and 4.59, respectively, p = 0.017. The presence of brain metastases and BRAF or NRAS mutation were independent factors for mortality in multivariate analysis.

Conclusions: In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases.

Keywords: BRAF; NRAS; immunotherapy; ipilimumab; melanoma.

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Conflict of interest statement

FDG has been a speaker at BMS and Novartis conference. PM had a consultant/advisory role for BMS, ROCHE Genentech, MSD, Novartis, AMGEN, Merck Serono, Pierre Fabre, and INCYTE. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Other authors do not declare any conflicts of interest.

Figures

Figure 1
Figure 1
Time scheme used for calculation of overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS).
Figure 2
Figure 2
Overall survival (OS) analysis. Kaplan–Meier survival curves in patients who received ipilimumab treatment after anti-PD-1 therapy failure, based on (A) presence of BRAF or NRAS mutation and (B) presence of brain metastases.
Figure 3
Figure 3
Progression-free survival (PFS) analysis. Kaplan–Meier curves in patients who received ipilimumab treatment after anti-PD-1 therapy failure based on (A) presence of brain metastases and (B) presence of pooled BRAF or NRAS mutation.
Figure 4
Figure 4
Post-progression survival (PPS) analysis. Kaplan–Meier survival curves in patients who received ipilimumab treatment after anti-PD-1 therapy failure based on the presence of BRAF or NRAS mutation.
See this image and copyright information in PMC

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