Author of

• 36512

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  P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36531

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    P84.22 - Outcomes of TKI Treatment in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Real-World Study in Argentina (ID 1622)

    00:00 - 00:00  |  Presenting Author(s): Diego Kaen
    • Abstract
    • Slides

    Introduction
    

    Uncommon epidermal growth factor receptor (EGFR) mutations account for 10–20% of all EGFR mutations and represent a heterogeneous molecular subgroup within exons 18–21. Sensitivity to EGFR tyrosine kinase inhibitor (TKIs) is variable and still not completely understood since it has not been evaluated in large prospective trials.

    Methods
    

    Advanced NSCLC patients harboring uncommon (other than L858R and exon 19 deletion) EGFR mutations at baseline tissue biopsy were selected from 13 centers in Argentina. EGFR mutations were retrieved from the medical oncology molecular laboratory databases. Clinical outcomes to first-line EGFR-TKIs were analyzed. Tumors with non-resistant uncommon EGFR mutations included other than L858R mutation, inframe deletions of exon 19, exon 20 insertions, and T790M. Complex mutations were defined as co-existing two or more distinct EGFR mutations.

    Results
    

    Among 45 patients included (median age 65 yrs; female 62%; ECOG 0-1 84%), most frequent EGFR-TKI used was afatinib (n=23), followed by erlotinib/gefitinib (n=13), and osimertinib (n=9). Distribution of tumors harboring at least one uncommon mutation was: exon 18 G719X n=21 (46.7%), 21 L861Q n=11 (24.4%), exon 20 T790M n=9 (20%), S768I n=5 (11.1%), exon 20 insertion n=2 (4.4%), and exon 19 pLys745_Ala750del n=1 (2.2%). Ten tumors (22.2%) presented complex mutations (6 classical+rare and 4 rare+rare), harboring two (n=8) and three (n=2) concurrent EGFR alterations. With a median follow-up of 25.7 months (mo) (95% CI 11.3-40.2), median PFS of first-line EGFR-TKI was 10.1 mo (95% CI 8.1-12.2) and median OS was 26.8 mo (95% CI 13.5-40.1). Clinical activity of afatinib in patients with non-resistant uncommon mutations was consistent according to the different alterations (L861Q ORR 63% and DCR 75%; G719X ORR 44% and DCR 89%; and S768I ORR 50% and DCR 50%; p=0.81 and 0.17, respectively). Of note, three patients harboring concurrent de-novo resistant T790M and a common sensitive EGFR mutation (L858R or exon 19del) achieved partial response using first and second-generation EGFR-TKIs. Similarly, afatinib also led response in a triple EGFR mutations tumor (exon 20 insertion + G719X + L858R). Patients with complex mutations tended to have a better response to first-line EGFR-TKI (ORR 90% [9/10]) than those with single non-resistant uncommon EGFR mutations (ORR 52% [14/27]) (p=0.06). Similarly, patients with complex mutations showed better OS (median not reached vs. 20.3 mo [95% CI 8.7-31.9], respectively; p=0.04).

    Conclusion
    

    NSCLC harboring uncommon EGFR mutations are a highly heterogeneous subgroup particularly underrepresented in clinical trials. Considerable clinical activity was observed to first-line EGFR-TKI in our study. Patients with complex mutations had significantly better survival.

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