Abstract 1047P
Background
AM is a rare melanoma subtype with poor prognosis. While retrospective data suggests low activity of PD1 alone, no data are available on the efficacy of combination PD1/CTLA4 in AM. AM primary site is associated with differences in tumour mutation burden, which may impact CPI activity. We examined the efficacy of CPIs in AM, and in primary site subgroups.
Methods
Patients (pts) with unresectable stage III/IV AM treated with at least one line of CPI (PD1 and/or ipilimumab (Ipi) were studied. Disease/patient characteristics and therapy were examined. Multivariable logistic and Cox regression analysis were conducted. Primary outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results
369 pts were included; median age at first diagnosis was 63yrs (20-88), 80% Caucasian, 53% male, 12% BRAF, 13% NRAS, 7% KIT mutant; 41 had received prior adjuvant CPI. Median time from primary diagnosis to development of advanced disease was 19.6 months [1.8-260.6]. Primary site of AM was 260 (70%) plantar, 25 (7%) palmar and 84 (23%) subungual. Excluding 41 pts who received adjuvant CPI, 1st line systemic therapy included 151 (46%) PD1, 51 (15%) Ipi, 54 (16%) combination CPI and 72 (22%) other therapies (e.g. chemotherapy, targeted therapy). At commencement of 1st-line therapy, 30% were stage M1c, 53% ECOG 0 and 19% had elevated LDH. Median follow up was 8.1yrs (7.68-10.66). ORR was highest with combination CPI; this remained significant in multivariate analysis (Table). PFS was significantly associated with 1st-line therapy, however PFS was not significantly different between PD1 and combination CPI (p=0.42) (Table). Median OS was 2.3yrs (95% CI 1.9-2.6) and did not vary by 1st-line therapy received (p=0.57). No outcome differences were found between primary sites. Table: 1047P
| OR = Odds ratio HR = Hazard ratio | PD1 (N=151) | CTLA4 (N=51) | PD1+CTLA4 (N=54) |
| ORR | 26% | 12% | 44% |
| Univariable OR | 1 | 0.43 (95%CI, 0.19-0.97), p=0.0009 | 2.24 (95%CI, 1.24-4.07), p=0.0023 |
| Multivariable OR | 1 | 0.45 (95%CI, 0.20-1.03), p=0.0015 | 2.38 (95%CI, 1.30-4.36), p=0.0015 |
| PFS (months) | 7.0 (95%CI, 5.3-1.5) | 4.9 (95%CI, 4.1-6.2) | 7.3 (95%CI, 4.9-13.2) |
| Univariable HR | 1 | 1.57 (95%CI, 1.15-2.14), p=0.0042 | 0.91 (95%CI, 0.66-2.14), p=0.56 |
| Multivariable HR | 1 | 1.64 (95%CI, 1.20-2.24), p=0.0019 | 0.87 (95%CI, 0.63-1.21), p=0.42 |
Conclusions
CPIs are active in pts with advanced AM, with superiority of combination CPI over PD1 alone in terms of ORR but not PFS or OS. Primary AM site did not impact CPI efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Bhave: Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Personal, Invited Speaker: Novartis. A. Zaremba: Financial Interests, Personal, Sponsor/Funding: Novartis; Financial Interests, Personal, Sponsor/Funding: Sanofi; Financial Interests, Personal, Sponsor/Funding: BMS. J.K. Schwarze: Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Personal, Sponsor/Funding: Amgen; Financial Interests, Personal, Invited Speaker: Novartis. All other authors have declared no conflicts of interest.