Doxycycline Prophylaxis Reduces Dacomitinib-Induced Toxicity

Prophylactic doxycycline could help to manage dermatological side effects associated with the second-generation tyrosine kinase inhibitor dacomitinib in late-stage non-small-cell lung cancer patients

medwireNews: A phase II trial shows that the incidence of select dermatological adverse events (AEs) of interest is lower in dacomitinib-treated patients with non-small-cell lung cancer (NSCLC) given prophylactic doxycycline compared with placebo.

Dacomitinib is an oral tyrosine kinase inhibitor (TKI) that targets several HER family enzymes; it is currently in development for the treatment of locally advanced or metastatic NSCLC. Although the side effects of TKIs are “rarely life-threatening”, say the researchers, they can negatively affect quality of life (QoL), leading to reduced adherence and thereby potentially jeopardising treatment efficacy.

The ARCHER 1042 trial was designed to evaluate the effect of prophylactic treatment on select dermatological AEs, diarrhoea and mucositis as well as patient-reported health-related QoL (HRQoL) in stage III or IVB NSCLC patients given dacomitinib 45 mg/day.

Doxycycline prophylaxis significantly reduced the incidence of select dermatological AEs of grade 2 or worse by half during the initial 8 weeks of dacomitinib treatment, with rates of 23.2% for the 56 participants randomly assigned to receive doxycycline 100 mg twice a day for 4 weeks and 46.6% for the 58 patients given matching placebo.

The incidence of all-grade dermatological AEs of interest was also lower in the doxycycline compared with the placebo arm, at 75.0% versus 79.3%, but this difference was not significant, as reported in the Annals of Oncology.

Using the Skindex-16 survey to assess HRQoL, the team found that compared with placebo, doxycycline treatment was associated with less deterioration in the total scores from baseline over the first 8 weeks of dacomitinib administration.

And treatment with doxycycline also led to a reduction in the proportion of patients who permanently discontinued dacomitinib owing to a treatment-emergent adverse event (7.1 vs 13.8%) and in the use of concomitant medication for select dermatological AEs (50.0 vs 65.5%).

“[T]his study showed that doxycycline is a promising prophylactic treatment in managing dacomitinib-induced grade ≥2 [select dermatological AEs of interest] and reducing deterioration in QOL with respect to dermatologic AEs”, conclude Mario Lacouture, from Memorial Sloan Kettering Cancer Center in New York, USA, and fellow investigators.

They also evaluated the effect of prophylaxis with topical alclometasone diproprionate cream 0.05% for 4 weeks in a separate cohort of 59 dacomitinib-treated patients. Although alclometasone reduced the incidence of all-grade and grade 2 or worse dermatological toxicities relative to placebo, the difference was not statistically significant.

Similar to doxycycline, patients given alclometasone reported less deterioration of total Skindex-16 scores, a smaller proportion discontinued dacomitinib as a result of toxicity (8.5 vs 13.8%) and the use of concomitant treatment for toxicities was also reduced (52.5 vs 65.5%).

This cohort of patients also received an oral probiotic VSL#3 – US patients took four capsules once a day and Korean patients one sachet daily. But this prophylactic treatment did not reduce the incidence of either all-grade or grade 2 or higher diarrhoea relative to placebo, nor did it improve mucositis scores, as assessed by the modified-Oral Mucositis Daily Questionnaire.

Reference

Lacouture ME, Keefe DM, Sonis S, et al. 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. Ann Oncol 2016; Advance online publication 10 June. doi:10.1093/annonc/mdw227

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016