KRAS mutations(m) in lung adenocarcinoma (AC) patients(p) receiving standard chemotherapy (ch) and immune checkpoint inhibitors (i-CI): Impact of KRAS clonality and coexisting TP53m

Date

08 Oct 2016

Session

Poster Display

Presenters

Nuria Pardo Aranda

Citation

Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383

Authors

N. Pardo Aranda1, F. Ruiz2, A. Martinez Marti1, S. Cedres1, A. Navarro Mendivil1, I. de la fuente1, A. Martinez de Castro1, A. Vivancos3, R. Dienstmann2, E. Felip1

Author affiliations

  • 1 Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 2 Oncology Data Science, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 3 Cancer Genomics Group, Vall d’Hebron Institute of Oncology, Barcelona/ES
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Background

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

Methods

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

Results

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 

Conclusions

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

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

VHIO

Disclosure

All authors have declared no conflicts of interest.

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