Cyramza® (ramucirumab): Varaktighet av blödning i fas 3 magcancerstudier

Study Designs

REGARD Study

The REGARD trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with metastatic or locally advanced gastric or GEJ adenocarcinoma treated previously with fluoropyrimidine- or platinum-based combination therapy with an ECOG PS of 0 or 1. Patients were randomly assigned in a 2:1 ratio (stratified by weight loss, region, and location of the primary tumor) to receive ramucirumab (8 mg/kg every 2 weeks) plus BSC (n=238) or placebo (every 2 weeks) plus BSC (n=117) until disease progression, unacceptable toxicity, withdrawal, or death.¹

RAINBOW Study

The RAINBOW trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with metastatic or locally advanced nonresectable gastric or GEJ adenocarcinoma following disease progression during or within 4 months after last dose of first-line platinum plus fluoropyrimidine combination chemotherapy with or without an anthracycline and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by region, measurable vs nonmeasurable disease, and TTP on first-line therapy) to receive ramucirumab (8 mg/kg days 1 and 15) plus paclitaxel (80 mg/m² days 1, 8, and 15) (n=330) or placebo (days 1 and 15) plus paclitaxel (80 mg/m² days 1, 8, and 15) (n=335) of a 28-day cycle until disease progression, unacceptable toxicity, withdrawal, or death.²

RAINFALL Study

The RAINFALL trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial in patients with metastatic gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease and an ECOG PS of 0 or 1. Patients were randomly assigned in a 1:1 ratio (stratified by primary tumor location, region, baseline ECOG PS, and disease measurability) to receive cisplatin (80 mg/m² IV day 1) and capecitabine (1000 mg/m² orally twice daily on days 1 to 14) plus either ramucirumab (8 mg/kg IV on days 1 and 8) or placebo. Treatment with 5-FU (800 mg/m²/day IV days 1 to 5) was allowed for patients not able to swallow capecitabine. Patients were treated until disease progression, intolerable toxicity, withdrawal or death.³

Please note, Cyramza is not approved in the first-line setting of gastric cancer.

Duration of Bleeding/Hemorrhage Events

The duration of bleeding among patients who experienced a bleeding/hemorrhage event in the phase 3 gastric/GEJ cancer studies is summarized in Table 1.

Table 1. Duration of Bleeding/Hemorrhage Among Patients Who Experienced a Bleeding Event in Phase 3 Gastric/GEJ Studies (Safety Population)⁴

Abbreviation: AE = adverse event.

^a N is the number or patients who experienced a bleeding/hemorrhage event. If a patient had more than one occurrence of the same event, the event with the longest duration was used in this analysis.

^b Events is defined as the number of patients that had their bleeding/hemorrhage event resolved by the cutoff date. If an AE was not resolved, then that AE was censored at the cutoff date.

References

1. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. http://dx.doi.org/10.1016/S0140-6736(13)61719-5

2. Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. http://dx.doi.org/10.1016/S1470-2045(14)70420-6

3. Fuchs CS, Shitara K, Di Bartolomeo, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(3):420-435. https://doi.org/10.1016/S1470-2045(18)30791-5

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

5-FU = 5-fluorouracil

ECOG = Eastern Cooperative Oncology Group

GEJ = gastroesophageal junction

IV = intravenous

PS = performance status