Ito, Y., Karayama, M., Inui, N., Kuroishi, S., Nakano, H., Nakamura, Y., ... Chida, K. (2014). Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer (Amsterdam, Netherlands), 84(3), 259–264. 

To evaluate the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist, and dexamethasone compared to standard therapy with a 5-HT3 receptor antagonist and dexamethasone

Chemotherapy-naïve patients receiving a carboplatin-based therapy were randomized to standard antiemetic regimens of a 5-HT3 receptor antagonist plus dexamethasone or a triple antiemetic regimen of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant.  

• N = 134  
• AGE = ≥ 20 years
• MALES: 82%, FEMALES: 18%
• KEY DISEASE CHARACTERISTICS: Chemotherapy-naïve patients with stage IIIB or IV ​non-small-cell lung cancer (NSCLC) who received moderately emetogenic, carboplatin-based chemotherapy (either carboplatin/taxol or carboplatin/pemetrexed)
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria: nausea and vomiting within 24 hours or use of antiemetic agents within 48 hours before administration of chemotherapy; use of pimozide; uncontrolled diabetes mellitus; asymptomatic brain metastasis; GI obstruction; or an active gastric ulcer

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

Multi-center, randomized, open-label, parallel-group, phase-II trial

Daily questionnaire regarding the frequency of vomiting and scoring of nausea during five days. Physicians recorded any additional antiemetic therapies used during the study period.

The aprepitant group had a better overall complete response (CR) of 80% (95% CI 69%–88%); the control group had a CR rate of 67% (95% CI 55%–77%). The difference is not significant. Rescue antiemetics were given to 15% of the aprepitant group and 28% of the control group. Adding aprepitant to patients receiving carboplatin/pemetrexed (with or without bevacizumab) had an overall CR of 84% in the aprepitant group versus 57% in the control group and a 87% CR in the aprepitant group versus 59% in the control group in the delayed phase of chemotherapy. The aprepitant group had a reduced need for rescue antiemetics compared to the control group (16% versus 36%, p = 0.04). Adding aprepitant to patients receiving carboplatin/paclitaxel did not reduce the use of rescue antiemetics.

Triple antiemetic therapy did not demonstrate a significant improvement in CR and decrease in chemotherapy-induced nausea and vomiting events in the overall and delayed phases of therapy when compared to standard use of 5-HT3 and dexamethasone as an antiemetic regimen in patients with stage IIIB–IV NSCLC being treated with carboplatin-based chemotherapy (considered moderately emetogenic chemotherapy). The addition of aprepitant to the regimen of carboplatin/pemetrexed (with or without bevacizumab) improved the overall response rate and delayed phase response in addition to decreasing use of rescue antiemetics.

• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions are not described that would influence results.
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: High percentage of male to female study participants overall may reduce generalizability to general population. Patients on carboplatin/paclitaxel regimen received a high-dose steroid (12 mg) IV to prevent anaphylaxis; this may influence the effectiveness of the antiemetic regimen.

There may be benefit to adding aprepitant to antiemetic regimens for patients with NSCLC being treated with carboplatin/pemetrexed. This benefit was not demonstrated when aprepitant was added to carboplatin/paclitaxel regimens.