Question Over Ramucirumab in First-Line Gastric Cancer

Roxanne Nelson, RN, BSN

January 19, 2018

SAN FRANCISCO — Adding the antiangiogenesis agent ramucirumab (Cyramza, Eli Lilly) to first-line chemotherapy conferred a significant  reduction in the risk for disease progression or death among patients with metastatic gastric or gastroesophageal junction adenocarcinoma, according to results of the RAINFALL trial.

The study met its primary endpoint of progression free survival (PFS), said  lead author, Charles S. Fuchs, MD, MPH, director of Yale Cancer Center, New Haven, Connecticut.

"But it did not confer any improvement in overall survival," he noted.

Dr Fuchs presented the results of his study here at the Gastrointestinal Cancers Symposium (GICS) 2018.

Discussing the results at the meeting, Stephen Leong, MD, from the University of Colorado Cancer Center, Denver, noted that the improvement in PFS, from a median of 5.4 months with placebo to 5.7 months with ramucirumab (hazard ratio [HR], 0.75; P = .011), amounted to just 9 days.

Dr Leong also noted that there are financial aspects to consider. "The median duration of therapy was 19 weeks," he said. "Here in the US, one dose costs $7456 and that does not include the infusion or the port."

Assuming that the patient doesn't have any treatment delays, the patient will receive nine treatments, at a cost of $60,000, he added.

Efficacy Seen in Second-Line

Dr Fuchs explained that the study in the first-line setting was conducted  because two previous trials showed an improvement in overall survival in the second-line setting.

Ramucirumab is already approved for use in the second-line treatment setting of advanced stomach cancer and malignancies located at the junction of the stomach and esophagus.

"Two independent placebo-controlled randomized trials demonstrated significant improvements in overall survival with ramucirumab as a single agent in the REGARD study and in combination with paclitaxel in the RAINBOW study," Dr Fuchs said.

"Given these documented benefits of ramucirumab in second-line treatment, we examined the safety and efficacy of ramucirumab in combination with first-line chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma."

No Overall Survival Benefit

In this study, Dr Fuchs and colleagues randomly assigned 645 treatment-naive patients with metastatic gastric or gastroesophageal junction adenocarcinoma to ramucirumab (8 mg/kg intravenously on days 1 and 8; n = 326) or placebo (n = 319) every 21 days. All patients received capecitabine or 5-fluorouracil plus cisplatin for up to six cycles, and treatment was continued until disease progression, toxicity, or other reasons.

Tumor assessments were performed at baseline and every 6 weeks thereafter.

The primary endpoint of the study was PFS based on investigator assessment. Secondary endpoints included overall survival, objective response, and quality of life.

RAINFALL met its primary endpoint of improving PFS, as already noted above.

However, there was no overall survival benefit for ramucirumab vs placebo (median, 11.2 vs 10.7 months; HR, 0.96; P = .68).

There was also no significant difference in overall response rate in the intent-to-treat population: 41.1% for ramucirumab vs 36.4% for placebo.

Possible Survival Benefit?

In an exploratory analysis, the authors examined the effect of post-study ramucirumab on overall survival, as measured from the start of first-line therapy. Patients who received post-study ramucirumab appeared to experience longer survival.

"Those who were randomized to first-line ramucirumab and then continued on post-study ramucirumab experienced a median overall survival of 16.2 months," Dr Fuchs said.

This is in comparison to 13 months for patients who had been randomly assigned to placebo and who did not use post-study ramucirumab.

No new safety signals were observed with ramucirumab. Grade 3 or higher adverse events reported with ramucirumab included neutropenia (26.3% ramucirumab vs 27% placebo), anemia (12.1% vs 14%), and hypertension (9.9% vs 1.6%). Ramucirumab was associated with a modestly higher rate of gastrointestinal perforation and proteinuria, Dr Fuchs noted.

The study was funded by Eli Lilly and Company. Dr Fuchs reports a consulting or advisory role with Lilly, Sanofi, Bayer, Merck, Entrinsic Health, Five Prime Therapeutics, Agios, Gilead Sciences, Dicerna, Merrimack, Taiho Pharmaceutical, KEW, and Genentech/Roche; several coauthors also report relationships with industry as noted in the abstract. Dr Leong disclosed that he receives research funding from Eli Lilly, the sponsor of this study.

Gastrointestinal Cancers Symposium (GICS) 2018. Abstract 5. Presented January 18, 2018.

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