Ipilimumab After PD-1 Inhibition Failure Among Patients With Metastatic Melanoma

A single-center real-world study found that the, while ipilimumab in the second line may be an effective therapy for patients with BRAF/NRAS-wildtype metastatic melanoma, those patients who are BRAF- or NRAS-mutated or who have brain metastases may require more careful evaluation.

According to Sofia Verkhovskaia, MD, IDI-IRCCS, Rome, Italy, and coauthors, wrote that when the first-line monotherapy with a PD-1 inhibitor fails for a patients with metastatic melanoma “there are currently no standard second-line choices.” In the absence of clinical trials, they added, “ipilimumab represents a possible alternative treatment.” The goal of this study was to “estimate the impact of NRAS and BRAF mutations on the [overall survival], [progression-free survival], post-progression survival (PPS), and [objective response rate].”

There were 44 patients with inoperable or metastatic melanoma included in this trial, of which there were 28 with BRAF-wildtype, 9 BRAF-mutated, and 7 NRAS-mutated identified. All patients received ipilimumab in any line of treatment following failure on PD-1 inhibitor therapy between July 2017 and May 2023. The primary end point was overall survival (OS) with secondary end points including progression-free survival (PFS), PPS, and ORR.

The median OS for the overall study population was 14 months: 23.2 months for patients with BRAF-wild-type, 5.3 months for BRAF-mutated patients, and 4.5 months for NRAS-mutated patients. This represents a significant difference in OS between those patients who were wildtype and those with BRAF- or NRAS-mutated (P = .017). Dr Verkhovskaia et al, noted, “BRAF and NRAS mutations were independent risk factors for OS, after controlling for sex and the presence of brain metastases.”

There was a median PFS of 3.2 months for all patients, with 3.3 months for BRAF-wildtype patients and 2.4 months for pooled BRAF-/NRAS-mutated patients (P = .033). PPS was significantly higher among patients with BRAF-wildtype (11.7 months) compared to those with BRAF- (2.1 months) or NRAS-mutated (0.0 months; P = .002). Additionally, there were 8 patients with BRAF-wildtype who had a partial response, 2 patients with stable disease and 17 patients with progressive disease as the best result. Among BRAF-mutated patients, 8 patients showed progressive disease as best response with 1 patients achieving a partial response. Among the NRAS-mutated patients, 5 patients had progressive disease, 1 patient achieved a partial response, and 1 achieved a complete response.

Dr Verkhovskaia et al, concluded, “a careful evaluation should be performed by clinicians when prescribing ipilimumab as treatment after the failure of therapy with [PD-1 inhibition],” particularly for “patients with activating BRAF mutations who have been pre-treated with BRAF and MEK inhibitors, as well as NRAS-mutated patients,” as well as patients with brain metastases. They went to write, “Ipilimumab treatment could be of great value in patients with BRAF/NRAS-wildtype melanoma and without brain metastases, with several benefits to long-term survival, although a larger dataset is needed for a more precise indication.

Source:

Verkhovskaia S, Falcone R, Romana Di Pietro F, et al. Survival of patients with metastatic melanoma treated with ipilimumab after PD-1 inhibitors: A single-center real-world study. Cancers. 202416(19):3397. doi:10.3390/cancers16193397