Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer

• B. Ricciuti ^[1] ; M. Brambilla ^[2] ; A. Cortellini ^[3] ; A. De Giglio ^[1] ; C. Ficorella ^[3] ; A. Sidoni ^[5] ; G. Bellezza ^[5] ; L. Crinò ^[4] ; V. Ludovini ^[1] ; S. Baglivo ^[1] ; G. Metro ^[1] ; R. Chiari ^[1]
  1. [1] Università di Perugia

     Università di Perugia

     Perusa, Italia

     
  2. [2] University of Milan

     University of Milan

     Milán, Italia

     
  3. [3] University of L'Aquila

     University of L'Aquila

     L'Aquila, Italia

     
  4. [4] Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

     Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

     Meldola, Italia

     
  5. [5] Division of Pathology and Histology, Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 5, 2020, págs. 708-716
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown.

    Methods Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status.

    Results Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03–2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27–2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12–4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis.

    Conclusion Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.