RASm the most frequent oncogene alteration in ADC is not directly targetable with agents currently available for clinical use.We studied the efficacy of ch and i-CI in RASm ADC and explored a potential effect of clonality of KRASm and coexisting KRAS/TP53m in outcome
Out of 250 AC p with targeted mut profiling (Sequenom/Amplicon Seq)63 RASm(25%) were eligible for retrospective analysis of clinical endpoints. Primary endpoints: to determine progression-free survival (PFS) on first-line platinum-based ch plus maintenance 2PFS on subsequent i-CI as single agent; OS in metastatic setting(metOS) Secondary endpoints: to correlate survival endpoints with the clonality of KRAS mut allele fractions (MAFs, adjusted for tumor purity in the sample) and coexisting TP53m
Median age was 58yrs (range 33-75) 35male(55%) 24(38%)metastatic at diagnosis and in remaining pts, median time from diagnosis to relapse was 10 months (7-16) 61p had KRASm tumors, most frequent variants being G12C(25) G12V(10) G12D(9) G12other(6) G13(6) Q61(5) while 2p had NRASm tumors (Q61) with coexisting TP53m in 17/31(55%) Median KRAS MAF was 0.44( 0.32-0.55) with no differences if primary tumor (0.42 n = 36) or metastatic site biopsy (0.41 n = 5).19% of samples had MAFs
RAS mutated AC p have favorable outcomes when exposed to standard ch and i-CI.The majority of samples present KRAS MAFs suggesting clonal (truncal) events.TP53m is the most common coexisting driver alteration.In our exploratory cohort,these factors did not impact treatment benefit of ch, i-CI or survival in the metastatic setting
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All authors have declared no conflicts of interest.