Second-line options in patients with BRAF-negative advanced melanoma following progression on anti-PD-1 therapy: A retrospective observational study from two centers in Russia.

Abstract

e21519 Background: While anti-PD-1 is the first-line (1L) standard for BRAFwt advanced melanoma (aM), disease progression (PD) occurs in over half of patients, requiring second-line (2L) strategies. The ipilimumab/nivolumab (Ipi/nivo), though frequently used in 2L, is limited by toxicity and financial burden, and its ability to overcome resistance to prior immunotherapy is unclear. We aimed to assess different 2L options and the potential of Ipi/nivo based on prior anti-PD-1 response. Methods: A retrospective observational study approved by the IRB was conducted at two Russian centers: N.N. Blokhin NMRCO and Moscow Oncology City Hospital 62. We included all pts aged ≥18 yrs with BRAFwt aM who progressed on anti-PD-1 and were treated or consulted in these centers in 2023. We assessed the PFS from the start of 2L to PD, OS from the start of 1L (OS1) and 2L (OS2) to death from all pts and PFS, OS1 and OS2 in the Ipi/nivo group regardless of previous best response to anti-PD-1: complete and partial response (CR and PR), stable disease (SD), PD. Results: A total of 86 pts were included, 38 (44,2%) male and 48 (55,8%) female, with a mean age of 61,2 yrs. The 2L options are presented in the Table below. 4 patients were re-administered anti-PD-1 in the 2L after PD and local treatment for PD. mPFS was higher in the Pem/Len group but no statistically significant differences (SSD) were observed between all groups for either PFS, OS1 or OS2. Among pts in the Ipi/nivo group nearly half progressed on anti-PD-1 at the first CT/MRI assessment (see the Table). Only 6,2% had an objective response to anti-PD-1 earlier (CR+PR). Generally, the PD group had the lowest survival rates (the exception of the PR group of 2 pts), although no SSD were found between groups in PFS, OS1, and OS2. Conclusions: Ipi/nivo remains the primary 2L option for BRAFwt aM. No SSD between subgroups were found. The highest PFS in the Pem/Len may be attributed to the mechanism of action of this combination. Previous responses to anti-PD-1 in 1L may influence the effect of Ipi/nivo. These results need to be interpreted with caution given its retrospective nature and small number of pts in groups. Total n=86 (100%) Ipi/nivon=65 (75,6%) CTX10 (11,6%) Pem/Len5 (5,8%) Anti-PD-14 (4,7%) Trame (NRAS+)2 (2,3%) mPFS, mo 3,5 (3,0 - 6,2) 2,63 (2,3 - Na) 11,7 (3,6 - Na) 4,65 (3,5 - Na) 1,15 (1,0 - Na) mOS2, mo 21,8 (17,5 - 34,3) 8,8 (4,7 - Na) 11,5 (Na - Na) 13,7 (10,9 - Na) 1,3 (Na - Na) mOS1, mo 36,2 (28,1 - 55,4) 13,8 (12,3 - Na) Na 58,4 (21,8 - Na) Na (21,9 - Na) Survival in Ipi/nivo (n=65) Best response on anti-PD-1 in 1L CR2 (3,1%) PR2 (3,1%) SD20 (30,8%) PD32 (49,2%) Unk9 (13,8%) mPFS, mo 3,8 (3,8 - Na) 5,9 (5,8 - Na) 5,1 (2,8 - 10,2) 3,0 (2,6 - 6,2) 3,9 (2,8 - Na) mOS2, mo 34,3 (34,3 - Na) 6,7 (6,7 - Na) 32,1 (17,9 - Na) 18,2 (13,43 - 31,6) 39,1 (9,8 - Na) mOS1, mo 65,9 (65,9 - Na) 23,4 (23,4 - Na) 48,1 (30,8 - Na) 24,6 (20,9 - 36,9) 55,4 (31,8 - Na)