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F. Ohyanagi
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-072 - Dacomitinib Versus Gefitinib for First-Line Treatment of Advanced EGFR+ NSCLC in Japanese Patients (ARCHER 1050) (ID 8476)
09:30 - 09:30 | Author(s): F. Ohyanagi
- Abstract
Background:
Second-generation EGFR tyrosine-kinase inhibitor dacomitinib has shown encouraging activity as first-line therapy in patients with EGFR-activating mutation-positive (EGFR[+]) advanced NSCLC. We performed the first randomized, open-label phase 3 trial comparing dacomitinib with gefitinib as first-line therapy (NCT01774721) which demonstrated a clinically meaningful and statistically significant benefit of dacomitinib versus gefitinib (PFS per IRC: HR, 0.59 [95%CI, 0.47–0.74]; 1-sided P<0.0001; median PFS, 14.7 vs 9.2 months). We present results from Japanese patients enrolled in this ongoing study.
Method:
Patients with newly diagnosed stage IIIB/IV recurrent NSCLC harboring an EGFR-activating mutation (exon 19 deletion or exon 21 L858R ± exon 20 T790M) were randomized 1:1 to once-daily oral dacomitinib 45 mg or gefitinib 250 mg until disease progression or discontinuation. Patients with CNS mets excluded. Stratification was by race and EGFR mutation subtype. The primary endpoint was progression-free survival (PFS) per blinded independent review committee (IRC).
Result:
Among 452 patients enrolled in ARCHER 1050, 81 were Japanese. Slight imbalances in baseline characteristics were observed (Table). PFS and duration of response improvement in Japanese patients was consistent with global results.
Objective response rates per IRC were similar (dacomitinib, 75.0% [95%CI, 58.8–87.3]; gefitinib, 75.6% [95%CI, 59.7–87.6]; 2-sided P=0.9579). Overall survival data are not mature. All 81 patients received study treatment. No grade 4/5 adverse events (AEs were observed with dacomitinib, while 3 grade 4 AEs and 1 grade 5 AE (disease progression) occurred with gefitinib. The most common grade 3 AEs were dermatitis acneiform (27.5%) and paronychia (22.5%) with dacomitinib and alanine aminotransferase increased (12.2%) and abnormal hepatic function (7.3%) with gefitinib. No new safety signals were identified.Japanese Intention-to-Treat Population Dacomitinib (n = 40) n (%) Gefitinib (n = 41) n (%) Unstratified HR [95% CI] 1-sided p-value Male 15 (37.5) 20 (48.8) Age, years <65 ≥65 19 (47.5) 21 (52.5) 15 (36.6) 26 (63.4) Smoking status Never smoked Ex-smoker Smoker 19 (47.5) 20 (50.0) 1 (2.5) 24 (58.5) 16 (39.0) 1 (2.4) ECOG PS 0 1 28 (70.0) 12 (30.0) 21 (51.2) 20 (48.8) Median, months Median, months PFS per IRC 18.2 (95% CI, 11.0–31.3) 9.3 (95% CI, 7.4–14.7) 0.54 (95% CI, 0.31–0.95) P=0.0141 PFS per INV 18.3 (95% CI, 14.6–22.1) 10.2 (95% CI, 7.3–16.9) 0.61 (95% CI, 0.36–1.04) P=0.0334 DoR per IRC in responders # of responders=30 17.5 (95% CI, 10.2–34.3) # of responders=31 8.3 (95% CI, 5.6–12.9) 0.44 (95% CI, 0.22–0.84) P=0.0056 CI, confidence interval; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; INV, investigator assessment.
Conclusion:
Dacomitinib significantly improved PFS and duration of response over gefitinib in first-line treatment of Japanese patients with advanced EGFR[+] NSCLC, with a manageable safety profile.
