1118P - Real-world treatment patterns and outcomes among patients with BRAF+ metastatic melanoma refractory to first-line immunotherapy

Background

Many patients with BRAF+ metastatic melanoma (MM) experience tumor progression during first-line (1L) immunotherapy (IO). This real-world study evaluated the characteristics, treatment patterns, and outcomes among BRAF+ MM patients who experienced disease progression while on 1L IO.

Methods

This retrospective cohort study used Flatiron Health data from 1/1/2014 to 9/30/2021. Included patients were age ≥18 years with BRAF+ MM and were 1L IO-refractory, defined as having documented disease progression within 6 months of 1L IO initiation. Therapy use post-progression was defined as 2L, regardless of whether it was a new therapy or the same as 1L. Patient characteristics and treatment patterns were evaluated descriptively. The Kaplan-Meier method was used to describe overall survival (OS) and time to progression or death (TTPD) in patients who continued to receive IO (2L IO) and those who switched to targeted therapy (2L TT), from the start of 2L therapy.

Results

A total of 325 patients (mean age 60 years, 65% male) were included. Median time from 1L IO initiation to first disease progression was 64 days. Post-progression, 157 patients (48%) were treated with 2L IO within a median of 0 days and 83 (26%) initiated 2L TT within a median of 13 days. The median duration of 2L therapy for patients treated with 2L IO and 2L TT was 127 vs 182 days, respectively. Patients on 2L IO had improved median OS compared to those who received 2L TT (27.2 vs 10.5 months; p<0.0001) as well as improved time to next progression at 1 (32 vs 11%) and 2 years (23 vs 2%). Median TTPD was similar for patients treated with 2L IO and 2L TT (4.1 vs 4.8 months; p=0.078), despite patients receiving 2L TT having evidence of more severe disease (higher ECOG, elevated lactate dehydrogenase, and more liver metastases).

Conclusions

Outcomes among patients with 1L IO-refractory BRAF+ MM are poor and many patients progress on 2L therapy. While 2L IO appeared to lead to more durable treatment responses for some patients, 2L TT was associated with a similar TTPD despite patients having more severe disease. Earlier use of TT (i.e., 1L TT+IO combinations) should be considered for this group with especially poor prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

T. Truong, S. Chandra, Z. Eroglu: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis. L. Connolly, R. Shah: Financial Interests, Personal, Full or part-time Employment: Novartis. C. Byrne, J. Tang: Financial Interests, Institutional, Speaker, Consultant, Advisor: Novartis.