Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations

Background: Somatic CDKN2A and TP53 mutations are recurrent events in
melanoma, occurring in 13.3% and 15.1% of cases respectively and are
associated with poorer outcomes. It is unclear what effect somatic CDKN2A
and TP53 mutations have on the clinical outcomes of patients treated with
checkpoint inhibitors. Methods: All patients with cutaneous melanoma or
melanoma of unknown primary who received checkpoint inhibitor therapy and
underwent genomic profiling with the 50-gene Mayo Clinic solid tumor
targeted cancer gene panel were included. Patients were stratified
according to the presence or absence of mutations in BRAF, NRAS, CDKN2A,
and TP53. Patients without mutations in any of these genes were termed
quadruple wild type (Quad WT ). Clinical outcomes including median time to
progression (TTP), median overall survival (OS), 6-month and 12-month OS,
6-month and 12-month without progression, ORR and disease control rate
(DCR) were analyzed according to the mutational status of CDKN2A, TP53 and
Quad WT . Results: A total of 102 patients were included in this trial of
which 14 had somatic mutations of CDKN2A (CDKN2A mut ), 21 had TP53
mutations (TP53 mut ), and 12 were Quad WT . TP53 mut , CDKN2A mut and
Quad WT mutational status did not impact clinical outcomes including
median TTP, median OS, 6-month and 12-month OS, 6-month and 12-month
without progression, ORR and DCR. There was a trend towards improved
median TTP and DCR in CDKN2A mut cohort and a trend towards worsened
median TTP in the Quad WT cohort. Conclusion: Cell cycle regulators such
as TP53 and CDKN2A do not appear to significantly alter clinical outcomes
when immune checkpoint inhibitors are used.