A natural question is whether both chemotherapy and ramucirumab can be administered concurrently in second-line advanced/metastatic gastric/GEJ adenocarcinoma therapy. Although not approved at this time for this indication, the combination of ramucirumab and paclitaxel was demonstrated to improve outcome compared with single-agent paclitaxel in the RAINBOW trial.
In this randomized phase 3 trial, 665 patients in this setting were randomly assigned 1:1 to paclitaxel with or without ramucirumab. Those patients receiving the combination had improved median survival (primary endpoint) of 9.6 months compared with 7.4 months with single-agent paclitaxel (HR = 0.81; P = 0.02). 2
As many patients are not well enough to receive third-line therapy, combining ramucirumab and chemotherapy in the second-line setting may be a natural step for some patients, although it is not currently approved as such.
In summary, the approval of ramucirumab as a single agent in previously treated advanced/metastatic gastric/GEJ adenocarcinoma is a welcome addition to the therapeutic armamentarium in this disease. Oncologists now have a few second-line options, including ramucirumab monotherapy and taxane or irinotecan chemotherapy, or the combination of ramucirumab and a taxane.
Although ramucirumab is not currently approved in combination with chemotherapy, supportive data from the RAINBOW trial and the reality that many patients are not well enough for third-line therapy may make this an attractive option for some patients. This is a welcome conundrum to have!
- 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.
- Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). J Clin Oncol. 32, 2014 (suppl 3; abstr LBA7).