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Found 1 Presentation For Request "124P"
124P - KRAS mutated (mt) Non-small cell lung cancer (NSCLC) and response to antiPD-1/PD-L1 regarding co-mutational status and assessment of KRAS mutation on plasma or tissue biopsy
- E. Corral de la Fuente (Madrid, Spain)
- E. Corral de la Fuente (Madrid, Spain)
- J. Soto Castillo (Madrid, Spain)
- A. Gómez Rueda (Madrid, Spain)
- Y. Lage (Madrid, Spain)
- M. Olmedo García (Madrid, Spain)
- E. Vida Navas (Madrid, Spain)
- J. Torres Jimenez (Madrid, Spain)
- P. Alvarez Ballesteros (Madrid, Spain)
- M. Lario (Madrid, Spain)
- A. Benito Berlinches (Madrid, Spain)
- P. Garrido Lopez (Madrid, Spain)
Abstract
Background
Kirsten Rat Sarcoma viral oncogene (KRAS) mt advanced NSCLC conforms a heterogeneous disease typically treated with cytotoxic chemotherapy in combination with immunotherapy (IT) or IT alone based on PD-L1 expression. Co-mutations, KRAS mt subtypes and the allelic frequency of mutant KRAS might help to select the best treatment option.
Methods
Patients (Pts) diagnosed with advanced KRAS mt NSCLC determined by ctDNA next-generation sequencing (NGS), tissue NGS or both, were identified in our institutional lung cancer molecular database between 2011 and 2020. We retrospectively reviewed the response rate (RR) defined by RECIST1.1, with antiPD-1/PD-L1 and the potential correlation with co-mutations and the assessment of KRAS mutational status based on plasma or tissue biopsy. Clinicopathological characteristics were collected. Stata 15.1 was used for the analysis.
Results
69 pts were identified among 264 KRAS mt NSCLC pts. The average age at diagnosis was 62 (39–80) years. 63.7% were male. The most common histology was adenocarcinoma (82.61%). Most of patients (73.85%) were smokers with more than 30 pack-year (py) and only 3% never smokers. PDL1 was known in 91% of patients (25% <1%, 26% 1–49%, 41% >50%). KRAS mt was determined by NGS in plasma (27.5%), tissue (45%), both (18.8%) or other non-NGS techniques (8.7%). 59.4% pts had co-mutations (65.8% in plasma), TP53 was the most common (18/40). KRAS G12C was the most frequent KRAS mutation subtype identified (42.03%). 54.89% pts received IT as 1-line (L) treatment, 42.03% as 2L and 3.08% as 3L. Pts without co-mutations had significantly lower response rate (RR) to IT (21.1% vs 50%, p = 0.048). Regarding assessment of KRAS mutational status on plasma vs tissue biopsy, there were no statistically significant differences in RR (38.7% vs 36.1%, p = 1). Our study was limited by its retrospective design and selection of patients with heterogeneous disease.
Conclusions
Co-mutational status of KRAS could be related to better response to IT. Further randomized trials are needed to evaluate the role of KRAS co-mutational status and KRAS assessment in plasma or tissue biopsy and outcomes with IT.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Garrido Lopez: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Bristol (BMS); Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy: GlaxoSmithKline (GSK); Advisory/Consultancy: Lilly; Advisory/Consultancy: Bayer. All other authors have declared no conflicts of interest.