Real-world experience of dacomitinib in EGFR mutated advanced NSCLC: A single center experience from India.

Abstract

e21043 Background: Dacomitinib is an irreversible tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) approved in advanced non-small cell lung cancer (NSCLC) with mutated EGFR. Literature on real world experience of dacomitinib is lacking, especially in patients (pts) with brain metastasis and uncommon EGFR mutation. Methods: This is single center retrospective study of EGFR mutated advanced NSCLC patients treated with dacomitinib between July’19 and Dec’20. All patients received dacomitinib at 45 mg once oral dose except few with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2-3 and elderly received 30 mg once daily. Clinicopathologic features, treatment details, toxicity and treatment outcome were recorded. Progression free survival was calculated from start date of dacomitinib till date of progression. All pts underwent re-biopsy with evaluation for EGFR T790M at progression. Results: Total 43 pts were treated with median age of 63 years (range:43-81) and M: F ratio of 22:21. 26 pts accessed the drug through early access program, 6 pts through clinical trial and rest through commercially available product. ECOG PS was 1 in 29 pts, 2 in 13 pts and 3 in 1 patient. Ten patients had brain metastasis (out of evaluated 38) and 9 received whole brain radiotherapy. Type of mutations was Del 19 in 27 pts, L858R in 12 pts, G719X in 2pts, and Del 19 + L858R, L861Q in one patient each. Histopathology types were – adenocarcinoma in 39 pts, adenosquamous in 2 pts, NSCLC-not otherwise specified and squamous histology in one patient each. Starting dose of dacomitinib was 45 mg in 34 pts and 30 mg in 9 pts. 39 pts had any grade of toxicity and 20 pts (47%) had any grade 2 & 3 toxicity- mostly diarrhea and acneiform skin rash. Total 18 pts (42%) required dose modification (all from 45 mg to 30 mg). 38 pts have evaluable response: complete response in 2, partial response in 34 and stable disease in 2 pts. 8 out of 10 pts with brain metastases had partial response. All three pts with uncommon EGFR mutation had partial response. Five pts underwent re-biopsy on subsequent progression (4 had Del 19 and one had L861Q) and two developed EGFR T790M mutation. Six patients died (5 died of infection and one died of acute myocardial infarction). After a median follow-up of 13.8 months (range: 1.2-20.1), the median PFS not reached (95% confidence interval [CI]: 17.9, not reached) and 2-yr PFS was 57.5%. Conclusions: This is the largest experience of dacomitinib in EGFR mutated advanced NSCLC from Indian subcontinent. This is first reported activity of dacomitinib in pts with brain metastasis and uncommon EGFR mutation. Response rate was high and durable. 42% pts on 45 mg oral daily dose required dose modification due to toxicity. 30 mg once daily may be an optimum dose of dacomitinib in Indian pts.