Treatment pattern and outcomes in patients with uncommon or compound EGFR mutations in India: CRSF 2020-03 study.

Abstract

e21034 Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resulted in significant improvement in the outcomes of patients with activating EGFR mutations. But the ideal treatment of patients harboring uncommon, or compound mutations is not well defined. This multicentric audit was conducted to study the distribution, treatment pattern, and outcomes of patients with uncommon or compound EGFR mutations. Methods: This was a multicentric retrospective study that included patients with uncommon (mutations other than Exon 19 deletions and Exon 21 L858R) or compound (double or complex) mutations treated during the period of 2017-2020. Statistical analysis was done using SPSS version 20.0. Descriptive statistics were used wherever appropriate. Kaplan Meier Aanlaysis was performed for estimation of PFS and OS. Results: Total 99 patients with uncommon or compound mutations were included in the study. The median age was 55 years (25-82 years). Majority were males (n=65,67%) and 47 (47%) were smokers. Sixty-seven patients (68 %) had a single uncommon mutation and the remaining 32 (32%) had compound mutations. Most common mutations were exon 20 insertion (n=34, 35%) and T790M (N=16,16%). Other frequent mutations observed were exon 18 G719X (n=7,7%) and exon 21 L861Q (n=3,3%). Twenty-three patients (n=23,23%) were eligible only for best supportive care. Thirty-two patients (32%) received first-generation TKI, 30 patients (30%) received palliative chemotherapy and 11 patients (11 %) received Osimertinib. Gefitinib with chemotherapy was used in 2 patients and combination of Gefitinib with Afatinib was used in one patient. Overall response rate and clinical benefit rate with first line treatment was 23% and 35% respectively. Response could not be assessed in 14 patients. Median PFS was 5 months (95% CI 3.4-6.9) and median OS was 8.3 months (95% CI 3.3- 13). In patients who received any form of systemic treatment, median PFS was 6.2 months (95% CI- 3.3-9.1) and OS was 11 months (95% CI -8.9-13.9). Conclusions: The most frequent uncommon mutations in India are exon 20 insertion followed by compound mutations and exon 20 T790M mutation. Outcomes of patients with these rare mutations are dismal in the real world setting with the available treatment options.