Raftopoulos, H., Boccia, R., Cooper, W., O'Boyle, E., & Gralla, R.J. (2015). Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: Analysis by American Society of Clinical Oncology emetogenicity criteria. Future Oncology, 11, 2541–2551. 

To examine whether the post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC)

In the original study, patients were randomized 1:1:1 to receive APF530 500 mg subcutanous plus placebo IV, APR530 250 mg subcutaneous and palonosetron 0.25 mg plus placebo. The first objective was to establish noninferiority of APF530. For the second cycle, the placebos were dropped, and individuals who had been randomized to the palonsetron were randomly assigned to either 250 or 500 mg of APR530.

• N = Original study: 1,341 patients, secondary analysis: 1,299 patients (609 in the MEC group and 690 in the HEC group). Forty-two patients were dropped because they were reclassified as receiving regimens now considered less emetogenic than MEC. Of the remaining subjects, almost 50% were reclassified from MEC to HEC or HEC to MEC.  
• MEAN AGE = 60.3 years (MEC group), 53.4 years (HEC group)
• MALES: 24.8%, FEMALES: 75.2%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: The most common tumors were lung, ovarian, and breast.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: International study—United States, Europe, India

ACUTE PHASE OF CARE: Active antitumor treatment

Secondary analysis of a randomized, controlled study

Complete response (CR) was measured by no emetic episodes and no use of rescue medications during the acute and delayed phases of CINV after cycle one. Noninferiority was established if the confidence interval for the difference in CR was greater than 15%.

The results of this secondary analysis did not find significance difference between APF530 and palonsetron for acute and delayed CINV in patients receiving HEC and MEC regimens. There were no notable differences in the results of this study and the original analysis, except they found numerically higher CR rates in patients receiving MEC and lower CR rates in patients receiving HEC for all study arms.

The post hoc analysis presented here confirms the original findings of the APF530 phase III trial, that APF530 is an alternative to palonsetron for preventing acute and delayed CINV after MEC and HEC.

Post hoc analysis

The results of this study will not change the current use of slow-release granisetron (noninferior to palonsetron) for acute and delayed CINV after HEC and MEC, but confirms previous knowledge with new ASCO emetogenicity criteria.