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Addition of oxaliplatin to folinic acid-modulated fluorouracil extended survival in pancreatic cancer
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The addition of oxaliplatin to second-line treatment with folinic acid and fluorouracil significantly extended OS and time to progression in patients with advanced gemcitabine-refractory pancreatic cancer, according to results of a randomized, open-label phase 3 study.
The findings support the recommendation of the regimen as standard for this patient population, according to researchers.
The analysis included 168 patients aged 18 years and older treated at 16 institutions across Germany. All patients experienced disease progression during first-line monotherapy with gemcitabine (Gemzar, Eli Lilly).
Second-line treatment, which began within 4 weeks of progression on gemcitabine, was administered in 42-day cycles.
Researchers randomly assigned 91 patients to IV folinic acid 200 mg/m2 followed by a continuous IV infusion of fluorouracil 2,000 mg/m2 over 24 hours on days 1,8, 15 and 22. The other 77 patients received oxaliplatin 85 mg/m2 prior to folinic acid and fluorouracil on days 8 and 22.
Median follow-up was 54.1 months.
Patients assigned oxaliplatin demonstrated significantly improved median OS (5.9 months vs. 3.3 months; HR=0.66; 95% CI, 0.48-0.91) and significantly longer median time to progression (2.9 months vs. 2 months; HR=0.68; 95% CI, 0.5-0.94).
Researchers reported a higher rate of grade 1/grade 2 neurotoxicity (38.2% vs. 7.1%) among patients assigned oxaliplatin. Incidence of other adverse events were similar between treatment groups.
Disclosure: The researchers report research funding from Celgene and Eli Lilly, as well as consultant/advisory roles with Celgene, Eli Lilly and Fresenius.
Perspective
Back to TopSafi Shahda, MD
Pancreatic cancer continues to have poor prognosis, with a 5-year survival of 5%. Gemcitabine in comparison to 5-FU resulted in clinical benefit with marginal improvement in survival (Burris HA. J Clin Oncol. 1997;15:2403-2413). Since then, gemcitabine has become the standard of care for the treatment of metastatic pancreatic cancer.Several clinical trials evaluated gemcitabine in combination with cytotoxic chemotherapy and novel agents with negative results. Most recently, two randomized phase 3 trials demonstrated survival benefit of combination chemotherapy compared with gemcitabine alone (Conroy T. N Engl J Med. 2011;364:1817-1825. Von Hoff DD. N Engl J Med. 2013;369:1691-1703), changing the paradigm of first-line therapy in patients with good performance status.
Because gemcitabine represented the standard of care for more than a decade, several clinical trials addressed the role of chemotherapy post-progression on gemcitabine. Oettle and colleagues recently published the results of the CONKO-003 trial, which compared oxaliplatin plus 5FU/folinic acid with 5FU/folinic acid alone. The CONKO-003 study is the first randomized phase 3 study to demonstrate survival benefit comparing different regimens of chemotherapy in the second-line setting. It adds to the literature supporting the role of second-line chemotherapy, which mainly consisted of phase 2 studies (Yoo C. Br J Cancer. 2009;101:1658-1663. Ko AH. Br J Cancer. 2013;109:920-925. Hurwitz H. Abstract #4000. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago).
Although CONKO-003 was conducted at the time single-agent gemcitabine was the standard of care, patients with good performance status (ECOG 0 or 1) were unlikely to receive gemcitabine monotherapy. However, for patients who receive gemcitabine-based combination first-line therapy, it is reasonable to proceed with 5FU-based therapy or clinical trial enrollment upon progression.
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