Effects of Dose Modifications on the Safety and Efficacy of Dacomitinib for EGFR Mutation-Positive NSCLC
Invited conference paper presented and published in conference proceedings

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In patients with EGFR mutation-positive advanced stage NSCLC, first-line dacomitinib significantly improved PFS, OS, DoR and time to treatment failure vs gefitinib (ARCHER 1050; NCT01774721).1,2 Dacomitinib starting dose was 45 mg QD for all patients, with reductions to 30 or 15 mg QD permitted. We explored effects of dacomitinib dose reduction on safety and efficacy in this ongoing study.

Patients with newly diagnosed stage IIIB/IV or recurrent NSCLC harboring an EGFR mutation (exon 19 del or exon 21 L858R) randomized to dacomitinib received 45 mg PO QD. Study endpoints and protocol-defined dose reduction parameters were previously described.1 We evaluated reasons for dose reductions, and their effects on incidence and severity of common adverse events (AEs) and key efficacy endpoints (PFS, OS, ORR). Data cutoff dates: 17-Feb-2017 (OS), 29-Jul-2016 (other endpoints).

Overall, 150 (66.1%) patients dose reduced for AEs (87 and 63 reduced to 30 and 15 mg QD as lowest dose, respectively); most commonly for skin toxicities (62.6%) and diarrhea (14.0%). Median time to each successive dose reduction was ~12 weeks. Incidence and severity of AEs declined following dose reduction, including grade ≥3 diarrhea (11.3% before vs 4.0% after), dermatitis acneiform (15.3% vs 6.7%), stomatitis (3.3% vs 2.7%) and paronychia (7.3% vs 4.7%).

PFS was similar in dose-reduced and all dacomitinib-treated patients (Figure).
Median OS results were also similar (dose-reduced patients: 36.7 mo [95% CI: 32.6, NR]; all dacomitinib-treated patients: 34.1 mo [95% CI: 29.5, 37.7] as were ORRs (dose-reduced patients: 79.3% [95% CI: 72.0, 85.5]; all dacomitinib-treated patients: 74.9% [95% CI: 68.7, 80.4]).

Efficacy was similar in the dose-reduced patients and the overall study population. Incidence/severity of dacomitinib-related AEs decreased with dose reduction, thereby allowing patients to continue treatment.


Wu, et al. Lancet Oncol. 2017.

Mok, et al. J Clin Oncol. 2018.
All Author(s) ListTony S. Mok, Kazuhiko Nakagawa, Rafael Rosell, Ki Hyeong Lee, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Rolf Linke, Geeta Devgan, Eric I. Sbar, Susan Quinn, Tao Wang, Yi-Long Wu
Name of ConferenceWCLC 2018, 19th World Conference on Lung Cancer
Start Date of Conference23/09/2018
End Date of Conference26/09/2018
Place of ConferenceToronto
Country/Region of ConferenceCanada
Proceedings TitleJournal of Thoracic Oncology
Series TitleMini Oral Abstract Session
Number in SeriesAbst: MA26.11
Volume Number13
Issue NumberSuppl 10
PagesS454 - S454
LanguagesEnglish-United Kingdom

Last updated on 2020-04-07 at 00:41