CHICAGO -- Treatment with one of two biologic agents and standard chemotherapy produced a median survival of about 2.5 years among patients with advanced metastatic colorectal cancer, according to results of a long-term clinical trial.
Overall survival (OS) from the time of diagnosis among the 578 patients assigned to receive cetuximab (Erbitux) and chemotherapy was 29.9 months while OS was 29 months for the 559 patients treated with bevacizumab (Avastin) and chemotherapy (P=0.34), reported of the University of California San Francisco, and colleagues.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"The overall survival of 29 months establishes a new benchmark for clinical outcomes and that these outcomes should be expected in a variety of clinical settings, not just academic centers," Venook said during a press briefing at the American Society of Clinical Oncology annual meeting.
In addition, progression-free survival was 10.4 months for those assigned to the cetuximab combination and 10.8 months for patients who received the bevacizumab combination (P=0.55).
"What we can tell patients is that treatment with either FOLFOX or FOLFIRI, with either bevacizumab or cetuximab, are perfectly reasonable options," Venook said, adding that this data gives patients options in terms of which treatment they prefer based on adverse effects or convenience.
The study took 10 years to complete and included 11 interim analyses, as well as 14 protocol amendments, he said.
"We have just shown the tip of the iceberg with this study," Venook said. He added that his group will scrutinize the vast dataset to determine if there are differences in response rates, in duration of therapy, in specifics of surgery, and in the details of second-line therapy and other treatments.
Patients with KRAS wild-type metastatic adenocarcinoma of the colon or rectum were assigned to either the oxaliplatin (Eloxatin)-based FOLFOX chemotherapy treatment or the irinotecan (Camptosar)-based FOLFIRI chemotherapy regimen as preferred by the treating physician. They were then randomized to receive either cetuximab or bevacizumab.
The median patient age was 59 and 61% were male.
More than three-fourths of the physicians selected FOLFOX therapy in the study, Venook said, and this preference did limit chemotherapy comparison.
More extended genetic analyses may reveal that the FOLFOX regimen with either agent is the superior one, said co-investigator of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and principal investigator for the Southwestern Oncology Group.
"With chemotherapy and antibodies, we have never reached survival of 29 months," he told ѻý. "What makes this trial exceptional is that there has never been a trial that has collected so much blood, tumor, and plasma. We will have molecular profiling data that has never been done before. We are very excited about that opportunity to further dissect out these groups."
"While there may be a temptation to top-line this as a negative trial, this study sets an entirely new standard and a new high bar for clinical trials in advanced colorectal cancer," commented , ASCO president.
Lenz pointed out that it was particularly notable that the results were achieved in real-world hospitals and clinics. However, he cautioned that while the study shows "the overall improvement in treatment options, it still doesn't mean we know the best sequence of treatments or second-line therapies."
Disclosures
The study was funded by the NIH.
Venook disclosed relevant relationships with Bristol-Myers Squibb and Roche/Genentech.
Co-authors reported relationships with Roche/Genentech, Bayer/Onyx, sanofi-aventis, and Eli Lilly.
Hudis reported no relevant disclosures.
Primary Source
American Society of Clinical Oncology
Venook A, et al "CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab or cetuximab for patients with KRAS wild-type untreated metastatic adenocarcinoma of the colon or rectum" ASCO 2014; Abstract LBA3.