Abstract 1339P
Background
Dacomitinib, an irreversible tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), is 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 centre retrospective study of EGFR mutated advanced NSCLC pts treated with dacomitinib between July’19 and Feb’23. Clinicopathologic features, treatment details, toxicity and treatment outcome were recorded.
Results
Total 111 pts were treated with median age of 62 years (range: 39-82). ECOG performance status (PS) was 1 in 65 pts, 2 in 37 pts and 3 in 9 pts. 42 (38%, n=96) pts had brain metastasis and 21 pts received WBRT. Type of mutations was Del 19 in 66 pts, L858R in 35 pts, G719X in 4 pts, G719X and S768I in 2 pts, L861Q in 2 pts, and Del 19 + L858R, Exon 20ins + L858R in one patient each. Starting dose of dacomitinib was 45 mg in 43 pts and 30 mg in 68 pts (61%). Intracranial response (n=27) was – CR in 2 pts, PR in 18 pts, SD in 5 pts, and PD in 2 pts. 41 out of 52 pts underwent re-biopsy on progression, 17 pts had EGFR T790M mutation and 3 had small cell transformation. After a median follow-up of 19 months (95 CI: 14.4-23.2), the median PFS was 21.5 months (95% confidence interval [CI]: 18.7 – 26.2) and median overall survival (OS) was 31.2 months (95 CI: 23.4 – not reached). PFS was inferior in pts with brain metastases (p=0.003) and 30 mg starting dose (p=0.004), but not OS and neither with type of mutation or dose modification. 81(73%) pts had any grade of toxicity and 53 pts (47%) had any grade 2 & 3 toxicity. Total 25 pts (23%) required dose modification (Table). Table: 1339P
| Variables | Groups | HR | P |
| Progression-free survival | |||
| Brain metastases | Absent (n=54) | 1 | |
| Present (n=42) | 2.9 | 0.003 | |
| Not known (n=15) | 1.4 | 0.53 | |
| Type of mutation | Del 19 (n=69) | 1 | |
| L858R (n=34) | 1.6 | 0.12 | |
| Uncommon mutation (n=8) | 1.5 | 0.47 | |
| Starting dose of dacomitinib | 30 mg (n=68) | 1 | |
| 45 mg (n=43) | 0.9 | 0.004 | |
| Dose modification | Not required (n=88) | 1 | |
| Required (n=23) | 0.6 | 0.14 | |
| Overall survival | |||
| Brain metastases | Absent (n=54) | 1 | |
| Present (n=42) | 1.6 | 0.22 | |
| Not known (n=15) | 0.8 | 0.7 | |
| Type of mutation | Del 19 (n=69) | 1 | |
| L858R (n=34) | 1.5 | 0.32 | |
| Uncommon mutation (n=8) | 1.6 | 0.48 | |
| Starting dose of dacomitinib | 30 mg (n=68) | 1 | |
| 45 mg (n=43) | 1 | 0.8 | |
| Dose modification | Not required (n=88) | 1 | |
| Required (n=23) | 0.9 | 0.9 |
Conclusions
To best of our knowledge, this is largest real-world study of dacomitinib in mEGFR advanced NSCLC. Dacomitinib is active in pts with brain metastasis, uncommon EGFR mutation, in patients with poor PS, and at 30 mg starting dose. Dacomitinib showed very good PFS with manageable safety profile.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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