RAINBOW trial: Efficacy
CYRAMZA as a single agent, or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
RAINBOW Trial Design (N=665)1,5
The phase III RAINBOW trial evaluated the efficacy and safety of CYRAMZA + paclitaxel vs placebo + paclitaxel in patients with locally advanced or metastatic gastric or GEJ adenocarcinoma with disease progression on or after prior fluoropyrimidine- and platinum-containing chemotherapy. Major efficacy outcome measure was OS. Supportive efficacy outcome measures were PFS and ORR. All patients were ECOG PS 0 or 1. Prior to enrollment, 97% of patients had progressed during treatment or within 4 months after the last dose of first-line chemotherapy for metastatic disease. Twenty-five percent of patients had received anthracycline in combination with platinum/fluoropyrimidine therapy, while 75% did not. Patients were randomized 1:1 to CYRAMZA 8 mg/kg (n=330) or placebo (n=335) every 2 weeks (on days 1 and 15) of each 28-day cycle. Patients in both arms received paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle.1,5
Adding CYRAMZA to paclitaxel increased median OS by 30%1
versus placebo + paclitaxel - that could mean more time for your patients
RAINBOW OS: MEDIAN –MONTHS (95% CI)1
- The percentage of deaths at the time of analysis was 78% (256 patients) and 78% (260 patients) in the CYRAMZA plus paclitaxel and placebo plus paclitaxel treatment arms, respectively.1
SELECT IMPORTANT SAFETY INFORMATION
IMPAIRED WOUND HEALING
- CYRAMZA has the potential to adversely affect wound healing. CYRAMZA has not been studied in patients with serious or non-healing wounds.
- Withhold CYRAMZA for 28 days prior to elective surgery. Do not administer CYRAMZA for at least 2 weeks following a major surgical procedure and until adequate wound healing. The safety of resumption of CYRAMZA after resolution of wound healing complications has not been established.
40% of patients on CYRAMZA + paclitaxel survived 1 year or longer2
What could more time mean to your patients?
Survival Rate % (95% CI)
Adding CYRAMZA to paclitaxel significantly increased PFS vs paclitaxel + placebo1
RAINBOW PFS: MEDIAN –MONTHS (95% CI)1,3
- The percentage of events at the time of analysis was 85% (279 patients) and 88% (296 patients) in the CYRAMZA plus paclitaxel and placebo treatment arms, respectively1.
- 56 of 279 events in CYRAMZA-treated patients and 55 of 296 events in placebo-treated patients were deaths.
22% of patients on CYRAMZA + paclitaxel were progression free for 9 months or longer4
PFS Rate % (95% CI)4
SELECT IMPORTANT SAFETY INFORMATION
ARTERIAL THROMBOEMBOLIC EVENTS (ATEs)
- Serious, sometimes fatal, ATEs, including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia, occurred across clinical trials. In 2137 patients with various cancers treated with CYRAMZA, the incidence of all Grade ATE was 1-3%. Grade 3-5 ATE incidence was <1- 2%.
- Permanently discontinue CYRAMZA in patients who experience an ATE
Adding CYRAMZA to paclitaxel nearly doubled the response vs paclitaxel alone1,3
RAINBOW ORR: PERCENT OF PATIENTS (95% CI)*1
*2 complete responses in CYRAMZA-treated patients and 1 complete response in placebo-treated patients.
*ORR was defined as complete plus partial response. Disease progression and tumor response were assessed by investigators in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.13
RAINBOW Disease Control Rate
CYRAMZA plus paclitaxel had an 80% Disease Control Rate* (DCR) in the RAINBOW trial1
ORR was a pre-specified secondary efficacy endpoint in RAINBOW, with DCR being an exploratory endpoint. Exploratory endpoints were not adequately powered or controlled for type 1 error, and treatment differences observed cannot be regarded as statistically significant.
*Disease control rate was defined as complete response plus partial response plus stable disease.
RAINBOW Depth of Response
Tumor Response* in Intent-to-Treat (ITT) Population2-4
ORR was a pre-specified secondary endpoint and depth of response was an exploratory endpoint. Exploratory endpoints were not adequately powered or controlled for type 1 error, and treatment differences observed cannot be regarded as statistically significant.
*Tumor shrinkage was calculated based on the post-baseline tumor measurements change from baseline on target lesions per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (Eisenhauer et al. 2009). Patients included in the assessment had measurable disease.
†68 patients in the CYRAMZA + paclitaxel arm and 38 patients in the paclitaxel + placebo arm had tumor shrinkage of ≥40%. Patients who had non-measurable disease, no baseline tumor assessment, or no post-baseline tumor assessment were excluded from the tumor shrinkage analysis.
SELECT IMPORTANT SAFETY INFORMATION
- An increased incidence of severe hypertension occurred in patients receiving CYRAMZA. 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%.
- 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.
Time to deterioration in Quality of Life (QoL) was evaluated using the patient-reported EORTC QLQ-C30, a secondary endpoint in the RAINBOW trial1
The EORTC QLQ-C30 is a self-administered, cancer-specific QoL instrument that assesses global health status, functioning, disease- and treatment-related symptoms, and financial difficulties.2 The QLQ-C30 was developed for use in all cancer types and is not specific to any stage, intervention, or line of therapy. The results are reported as 15 scales, each with a range of 0 to 100 points, according to the EORTC scoring manual.3
Assessment and Analysis
Patients completed the QLQ-C30 at baseline, every 6 weeks following the first dose of study therapy until documentation of progressive disease, and at the end-of-therapy visit.
For each scale, time to deterioration was defined as the time from randomization to the first deterioration event, which was pre-specified as a worsening of ≥10 points from baseline. Time to deterioration was compared between arms using an unstratified Cox proportional hazards model. The analysis was conducted in the intent-to-treat (ITT) population.
Although a change of ≥10 points has been reported as meaningful for the QLQ-C304, the magnitudes of change for each of the 15 scales in patients with advanced/metastatic gastric cancer may differ.
At baseline, 98% of patients in each arm completed the QLQ-C30. Of the patients still receiving treatment in the study at weeks 6, 12, and 18, >83% of patients4 in each arm completed the QLQ-C30. Baseline scores were similar between arms.
Time to deterioration analyses in quality of life was evaluated using the patient reported EORTC QLQ-C30, a pre-specified secondary endpoint in the RAINBOW trial. This was not a gated endpoint and no specific hypothesis was tested, so results should only be interpreted descriptively. The analyses were not adequately powered to demonstrate any statistically significant effects and no adjustments were made for multiplicity.
Adverse events reported in clinical trials should not be compared with patient-reported outcomes.