ion with docetaxel at 75 mg/m2 every 21 days. Sites in East Asia administered a reduced dose of docetaxel at 60 mg/m2 every 21 days. Patients who discontinued combination therapy because of an adverse event attributed to either CYRAMZA/placebo or docetaxel were permitted to continue monotherapy with the other treatment component until disease progression or intolerable toxicity. Randomization was stratified by geographic region, gender, prior maintenance therapy, and ECOG PS.
Demographics and baseline characteristics were similar between treatment arms. Median age was 62 years; 67% of patients were men; 82% were White and 13% were Asian; 32% had ECOG PS 0; 73% had nonsquamous histology and 26% had squamous histology. In addition to platinum chemotherapy (99%), the most common prior therapies were pemetrexed (38%), gemcitabine (25%), taxane (24%), and bevacizumab (14%). Twenty-two percent of patients received prior maintenance therapy. Tumor EGFR status was unknown for the majority of patients (65%). Where tumor EGFR status was known (n=445), 7.5% were positive for EGFR mutation (n=33). No data were collected regarding tumor ALK rearrangement status.
Overall survival and progression-free survival were statistically significantly improved in patients randomized to receive CYRAMZA plus docetaxel compared to patients randomized to receive placebo plus docetaxel. Objective response rate (complete response + partial response) was 23% (95% CI: 20, 26) for CYRAMZA plus docetaxel and 14% (95% CI: 11, 17) for placebo plus docetaxel, p-value of <0.001. Efficacy results are shown in Table 8 and Figure 3.
Table 8: Randomized Trial of CYRAMZA plus Docetaxel versus Placebo plus Docetaxel in NSCLC
Abbreviations: CI = confidence interval
Figure 3: Kaplan-Meier Curves of Overall Survival - CYRAMZA plus Docetaxel versus Placebo plus Docetaxel in NSCLC
14.3 Colorectal Cancer
Study 4 was a multinational, randomized, double-blind, study of CYRAMZA plus FOLFIRI versus placebo plus FOLFIRI, in patients with mCRC, who had disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Patients were required to have ECOG PS 0 or 1 and to have disease progression within 6 months of the last dose of first-line therapy. A total of 1072 patients were randomized (1:1) to receive either CYRAMZA (n=536) at 8 mg/kg as an intravenous infusion or placebo (n=536), in combination with FOLFIRI: irinotecan 180 mg/m2 administered intravenously over 90 minutes and folinic acid 400 mg/m2 administered intravenously simultaneously over 120 minutes; followed by 5-fluorouracil 400 mg/m2 intravenous bolus over 2 to 4 minutes; followed by 5-fluorouracil 2400 mg/m2 administered intravenously by continuous infusion over 46 to 48 hours. Treatment cycles on both arms were repeated every 2 weeks. Patients who discontinued one or more components of treatment because of an adverse event were permitted to continue therapy with the other treatment component(s) until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival and the supportive efficacy outcome measure was progression-free survival. Randomization was stratified by geographic region, tumor KRAS status, and time to disease progression after beginning first-line treatment (<6 months versus ≥6 months).
Demographic and baseline characteristics were similar between treatment arms. Median age was 62 years; 57% of patients were men; 76% we |
