Metastatic Non-Small Cell Lung Cancer
REVEL trial: Progression-free survival
Statistically significant delay in disease progression in the ITT population1
Half of patients who received CYRAMZA + docetaxel achieved an estimated 4.5 months or longer PFS vs 3.0 months or longer for placebo + docetaxel1
REVEL PFS: Median—Months (95% CI)1
- The percentage of events at the time of analysis was 89% (558 patients) and 93% (583 patients) in the CYRAMZA + docetaxel and placebo + docetaxel arms, respectively1
- 126 of 558 events in CYRAMZA-treated patients and 109 of 583 events in placebo-treated patients were deaths1
REVEL Trial Design (N=1253)
The phase III REVEL trial evaluated the efficacy and safety of CYRAMZA plus docetaxel vs placebo plus docetaxel in patients with locally advanced or metastatic NSCLC with disease progression on or after platinum-based chemotherapy. Major efficacy outcome measure was overall survival. Supportive efficacy outcome measures were progression-free survival and overall response rate. All patients were required to have Eastern Cooperative Oncology Group performance status 0 or 1. Patients were randomized 1:1 to receive either CYRAMZA 10 mg/kg (n=628) or placebo (n=625), in combination with docetaxel* at 75 mg/m2 every 21 days.
*24 patients at East Asian sites received a starting dose of docetaxel at 60 mg/m2 every 3 weeks.
SELECT IMPORTANT SAFETY INFORMATION
- An increased incidence of severe hypertension occurred in patients receiving CYRAMZA. Across five clinical studies, excluding RELAY, in 1916 patients with various cancers treated with CYRAMZA, the incidence of all Grade hypertension ranged from 11-26%. Grade 3-5 hypertension incidence ranged from 6-15%. In 221 patients with NSCLC receiving CYRAMZA in combination with erlotinib in the RELAY study, the incidence of new or worsening hypertension was higher (45%), as was the incidence of Grade 3-5 hypertension (24%). Of the patients experiencing new or worsening hypertension in RELAY (N=100 CYRAMZA and erlotinib; N=27 placebo and erlotinib), 13% of those treated with CYRAMZA and erlotinib required initiation of 3 or more antihypertensive medications compared to 4% of patients treated with placebo and erlotinib.
- Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every two weeks or more frequently as indicated during treatment. Withhold CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA for medically significant hypertension that cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.
PFS results for CYRAMZA were consistent between the ITT population and patients with rapidly progressing disease* when added to docetaxel1,2
Post hoc exploratory subgroup analysis: Patients with rapid progression* on initial platinum-based therapy (≤12 weeks; n=209)2
REVEL Subgroup PFS: Median—Months (95% CI)2,3
- The percentage of events at the time of analysis in the CYRAMZA + docetaxel arm was 91% (101 patients) and 92.9% (91 patients) in the placebo + docetaxel arm2,4
REVEL Exploratory Analyses2,5,6
The REVEL trial was not adequately powered or error-controlled for subgroup analyses. Treatment differences observed in these subgroups cannot be regarded as statistically significant. The analyses described here were post hoc and exploratory.
*Rapidly progressing disease is defined as time to progression within 12 weeks after starting initial platinum-based treatment.2
CI=confidence interval; ECOG=Eastern Cooperative Oncology Group; HR=hazard ratio; ITT=intent-to-treat; mNSCLC=metastatic non-small cell lung cancer; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PS=performance status.