Ramucirumab adds to efficacy of chemotherapy in advanced gastric cancer

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.