Aprepitant for Cough Suppression in Advanced Lung Cancer: A Randomized Trial.

BACKGROUND: Although cough is a common and distressing symptom in patients with lung cancer, there is almost no evidence to guide treatment. Aprepitant, a centrally acting neurokinin-1 inhibitor, significantly decreased cough frequency in a pilot study. METHODS: Patients with advanced lung cancer and cough lasting over 2 weeks despite a cough suppressant were randomized 1:1 to aprepitant 125 mg orally on day 1 and then 80 mg orally on days 2 to 7 with physician's choice of antitussive; or to physician's choice of antitussive alone. Evaluation was at baseline and on days 3, 7, 9, and 12. The primary end point was subjective cough improvement on day 9, measured by the Visual Analog Scale and Manchester Cough in Lung Cancer Scale. Secondary end points included quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Lung Cancer-Specific Quality of Life Questionnaire and toxicity. RESULTS: Between 2017 and 2018, 128 patients were randomized. Median baseline cough duration was 90 days. Mean Visual Analog Scale scores (in mm) at baseline and day 9 were 68 and 39 in the aprepitant arm and 62 and 49 in the control arm, respectively (P < .001); mean Manchester Cough in Lung Cancer Scale scores at baseline and day 9 were 33 and 23 in the aprepitant arm and 30 and 25 in the control arm, respectively (P < .001). Overall QoL was not significantly different between the two arms; however, aprepitant led to a significant improvement in the cough-specific QoL domain (P = .017). Aprepitant did not increase severe adverse events. CONCLUSIONS: Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects. TRIAL REGISTRY: Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.