P76.75 Clinical Outcome and Toxicity Profiles of Patients with EGFR-mutation Positive Non-Small-Cell Lung Cancer

Abstract

Activating mutations of EGFR in advanced lung adenocarcinoma and its inhibition with specific tyrosine kinase inhibitors has been shown to generate clinically significant tumor responses. Treatment outcomes of advanced EGFR mutant lung carcinoma in Pakistani population are not previously reported. We conducted a study using the Real World Data (RWD) in patients with EGFR mutant advanced lung cancer treated at our institution. We evaluated clinical features, toxicity profile and outcome of these patients and compared it with those who were unable to receive TKI due to resource limitations. We identified 27 patients with advanced lung cancer harboring EGFR mutations that were treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2013 till April 2020. EGFR mutation detection was achieved by real time PCR. Data were collected through electronic medical record. Five patients were excluded from the analysis as they did not start treatment and were lost to follow-up. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves and log-rank analysis. Of the 22 patients analyzed, 54.5% were males and 45.5% were females. Twenty patients (90.9%) presented with de novo stage IV disease. Age ranged from 34-84 years. Frequency of Exon 19 deletion, Exon 21 L858R mutation, Exon18G7196 mutation and Exon 20 mutation was 50%, 32%, 9% and 4.5% respectively. One patient had compound Exon18G719X and Exon20S7681 mutation. 18.2% of patients had CNS metastasis at initial presentation. We identified 4 groups in our patient population. Group-1 consisted of patients who received first-generation TKI followed by third-generation TKI upon progression. Group-2 consisted of patients who received upfront first-generation TKI followed by chemotherapy upon progression. Group-3 consisted of patients who received upfront chemotherapy followed by a first-generation TKI upon progression and Group-4 consisted of patients who received upfront chemotherapy followed by second-line chemotherapy upon progression. These groups reflect the real world issues of TKI affordability in a Low Middle Income country (LMIC) such as Pakistan. Median PFS on first-line treatment (PFS1) was 10.7 months in the upfront chemotherapy group, versus 14.5 months in the upfront TKI group (p-value = 0.280). Median PFS on second-line treatment (PFS2) was 4.4 months in the chemotherapy group versus 23.7 months in the TKI group (p-value = 0.001). Median OS in Group 2, 3 and 4 was 20.0, 85.6 and 26.0 months respectively and not yet reached in Group 1 (p = 0.271). 27.8% patients developed grade I-II skin rash and diarrhea, 5.6% developed grade III-IV anemia, grade I-II neutropenia, and grade III-IV hyperbilirubinemia Within the constraints of a small sample size our real world data shows that the use of EGFR TKI in advanced EGFR mutant lung cancer is well tolerated in a Pakistani population. Use of EGFR TKI yields a superior PFS in both upfront and subsequent line of therapy which is consistent with the previously reported data. Preliminary overall survival favors superior outcome in the TKI group compared to chemotherapy alone or chemo-TKI combination groups.