Aprepitant a promising cough suppressant for advanced lung cancer patients

A week-long course of the centrally acting neurokinin-1 inhibitor aprepitant for treating cough in advanced lung cancer patients is effective and safe, producing significant improvements in cough severity and impact without increasing severe side effects, according to the results of a trial.

“The onset of action of aprepitant as a cough suppressant was relatively quick and the effect was sustained over time,” the investigators said, adding that the drug therefore “represents a new therapeutic option for patients with advanced lung cancer and cough that is not controlled by standard cough medications.”

In the trial, 128 patients were randomized to receive aprepitant 125 mg orally on the first day of treatment then 80 mg orally on days 2–7 with physician’s choice of antitussive (n=64) or to physician’s choice of antitussive alone (n=64). All patients had cough lasting >2 weeks (median, 90 days) despite a cough suppressant. Assessments were conducted on days 3, 7, 9 and 12.

The primary endpoint was subjective cough improvement at day 9, measured using the Visual Analog Scale (VAS) and Manchester Cough in Lung Cancer Scale (MCLCS). Mean VAS scores decreased from baseline by 29.18 mm in the aprepitant arm and by 13.63 mm in the control arm (p<0.001). The improvement seen with the neurokinin-1 inhibitor was greater than the accepted minimal important difference of 17 mm. [Chest 2019;doi:10.1016/j.chest.2019.11.048; J Thorac Dis 2014;6:S728-S734]

Mean MCLCS scores likewise decreased from baseline to day 9 in both arms, with a greater magnitude seen in the active treatment arm (from 33 to 23 vs from 30 to 25; p<0.001). Furthermore, significantly more patients on aprepitant achieved a decrease of at least one grade in their cough at end of study (50 percent vs 35 percent; p=0.058).

Overall quality of life (QoL), measured using the EORTC QLQ-C30 and QLQ-LC13, did not significantly differ between the two arms, but aprepitant produced a marked improvement in the cough-specific QoL domain (p=0.017).

Compared with the control, aprepitant was not associated with an increase in adverse events. The proportion of patients who had grade ≥3 adverse events was 15 percent in the active treatment arm and 16 percent in the control arm.

“In our study, we administered aprepitant for 7 days and found that patients continued to experience a sustained antitussive effect up to day 12 even after stopping [the drug],” the investigators said.

Furthermore, none of the patients required a dose reduction or medication hold for management of side-effects, considering that a 7-day dosing of aprepitant for cough is longer than the usual 3-day regimen for nausea and vomiting, they added.

“To the best of our knowledge, ours is the first randomized trial to demonstrate the benefit of a cough medication in patients with advanced lung cancer… An important drawback of our study was the length of time that aprepitant was administered for and the relatively short follow-up duration,” the investigators pointed out.

Although the study did not examine whether continuing aprepitant long term or repeating courses might help manage chronic cough in the population, the current data indicate that neurokinin-1 inhibitor represents a new treatment option for cough in advanced lung cancer patients, they said.