Cathy Eng, MD, on the FRESCO-2 Study in Metastatic Colorectal Cancer

The poster presentation that we'll be discussing today is regarding the overall survival of fruquintinib versus placebo after adjusting for subsequent anticancer therapy in patients with refractory colorectal cancer. As you may be aware, fruquintinib is a highly selective tyrosine kinase inhibitor, a VEGF receptors 1, 2, and 3. Recent indications were based upon approvals in the United States by the FDA, Europe, and Japan. And most recently, I believe it's Australia and Singapore has also received approval for this oral agent. FRESCO-2 was a clinical trial, which I served as the senior author on, which is looking at the role of a 2-to-1 randomization for the role of fruquintinib versus placebo in the refractory patient population. And that study was a positive study in regards to overall survival, and it also allowed patients to have received prior Lonsurf and/or regorafenib in that setting. And that was after a median of four lines of therapy. So this poster is basically focused on subsequent anticancer lines of therapy for patients who had progressed on fruquintinib or the placebo, and how did this impact overall survival? So a friendly reminder regarding the FRESCO-2 study, this was an international trial that involved over 124 hospitals and cancer centers across 14 different countries, and patients must have been exposed to prior fluoropyrimidine, oxaliplatin and irinotecan based therapy as well as anti-VEGF therapy, and if appropriate, anti-EGFR therapy if they were RAS wild type, and have had prior exposure to TAS-102, and regorafenib. In this post-hoc subgroup analysis, the impact of subsequent lines of chemotherapy on overall survival was assessed by excluding or censoring patients who received subsequent anticancer therapy. And basically, these are the results of those findings. So in short, 461 patients were in the investigational arm, 230 patients were in the placebo arm. In the investigational arm, the most common, subsequent anticancer lines of chemotherapy included 5-fluorouracil, regorafenib, oxaliplatin, capecitabine, irinotecan and bevacizumab. And the most common out of those were in order of fluorouracil, regorafenib, oxaliplatin and then bevacizumab in the investigational arms. The median age of the patient was comparable across all arms when comparing fruquintinib versus placebo in the subsequent anticancer therapy arm versus those without anticancer therapy. Once again, it was 213 patients with subsequent anticancer therapy provided, versus 478 patients without subsequent anticancer therapy provided. The majority of patients were Caucasian. The majority of patients were male patients overall. And the performance status was required on study to between 0 and 1. The primary tumor location for the majority of patients was colon and, no surprise, majority of patients also had liver metastasis in regards to sites of metastatic disease. Overall survival after adjusting for subsequent anticancer therapy was in favor of for fruquintinib regardless of the statistical approach that was evaluated. It was still in favor with a hazard ratio of 0.43 as well as between 0.43 and 0.48. Once again, I am not a statistician, I'm not going to go into depth regarding the statistical approach, but once again, it demonstrates that the role of anticancer therapy, it does not take away from the true benefit of fruquintinib versus placebo in this patient population. And in regards to toxicities that are commonly seen in this patient population, hypertension is a class effect of any anti-VEGF therapy. And this was the most common grade 3, 4 known adverse event, as well as followed by hand-foot-skin reaction, and then asthenia, which is exactly what we reported in the original FRESCO-2 study. In regards to the patients without subsequent anticancer therapy, hypertension still remained present in about 11% of patients, but asthenia as well as hand-foot-skin reaction in the fruquintinib arm. So once again, it's a class effect of this group of agents, but to much less degree if they had not received subsequent anticancer therapy. So basically, the overall safety profile of fruquintinib versus placebo was generally consistent with the original intent to treat population. And in short, basically these findings demonstrate that regardless of anticancer therapy provided, there is definite benefit of the fruquintinib versus placebo in our previously treated patient population.