A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer.

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.