December 19, 2019
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Switch to maintenance therapy ‘appropriate and beneficial’ in metastatic colorectal cancer

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Maintenance chemotherapy following initial treatment appeared to be more beneficial for patients with metastatic colorectal cancer than continuing a full induction regimen until disease progression, according to results of a meta-analysis of randomized clinical trials published in JAMA Oncology.

“Based on these findings, switching to a lighter, maintenance regimen of chemotherapy or even taking a break in treatment for some patients is appropriate, with reintroduction of full chemotherapy when the disease progresses,” Mohamad B. Sonbol, MD, clinical oncologist at Mayo Clinic in Phoenix, said in a press release. “The goal of therapy in metastatic colorectal cancer is to prolong life while preserving or improving quality of life. As most of these therapies are associated with side effects, it’s important to use treatments that achieve a maximum benefit with the fewest side effects.”

Patients with advanced metastatic colorectal cancer typically receive cytotoxic chemotherapy in combination with a molecularly targeted drug. How long to continue first-line induction chemotherapy after achieving maximum response, however, has been a subject of controversy because of toxicity that can occur after prolonged treatment.

Sonbol and colleagues analyzed 12 phase 2 or phase 3 randomized trials comprising 5,540 patients (age range, 23-85 years; 64.4% men) with metastatic colorectal cancer. Patients in the trials received initial cytotoxic chemotherapy, with or without a biologic, followed by observation, maintenance with bevacizumab (Avastin, Genentech), fluoropyrimidine or both, or continuation of the induction regimen until progression.

Seven trials included a control group that underwent observation, which was compared with bevacizumab in three trials, fluoropyrimidine in two trials, and fluoropyrimidine with bevacizumab in two trials.

Ten trials had induction regimens that included oxaliplatin with either capecitabine or fluorouracil and leucovorin. The two other trials used irinotecan-based therapy.

Duration of treatment among all trials ranged between 12 and 24 weeks.

OS and PFS served as the study’s outcomes of interest. Researchers used the DerSimonian and Laird random-effects model to pool the overall effect. They performed network meta-analysis using a random-effects consistency model to pool evidence from direct and indirect comparisons.

Results of this analysis showed no benefit of continuing full cytotoxic chemotherapy until progression compared with observation when analyzing PFS (HR = 0.71; 95% CI, 0.46-1.09) or OS (HR = 0.95; 95% CI, 0.85-1.07).

When compared with observation, maintenance therapy conferred a PFS benefit (HR = 0.58; 95% CI, 0.43-0.77) but no OS benefit (HR = 0.91; 95% CI, 0.83-1.01).

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All maintenance strategies, including fluoropyrimidine and fluoropyrimidine in combination with bevacizumab, demonstrated significant improvement in PFS compared with observation.

An analysis that ranked agents using surface under the cumulative ranking probabilities showed maintenance treatment had the highest likelihood of conferring improved PFS (67.1% for fluoropyrimidine, 99.8% for fluoropyrimidine with bevacizumab and 36.5% for bevacizumab) and OS (81.3% for fluoropyrimidine, 73.2% for fluoropyrimidine with bevacizumab and 32.6% for bevacizumab).

“Many chemotherapies that are used are initially beneficial in both shrinking and controlling the cancer,” Tanios S. Bekaii-Saab, MD, gastrointestinal oncologist at Mayo Clinic in Phoenix, said in a press release. “However, after a few months of therapy, the maximum benefit is usually achieved and the main focus should be on how to continue that benefit while minimizing side effects. This study confirms that switching to maintenance treatment is appropriate and beneficial, with introduction of full chemotherapy later upon progression of the disease.” – by John DeRosier

Disclosures: Bekaii-Saab reports advisory/consultant roles with Amgen, Array, Bayer, Genentech/Roche, Incyte, Imugene, Immuneering, Ipsen, Pieris and Pfizer, and serving on independent data monitoring committees for Armo, AstraZeneca, Merck and Silajen. Sonbol reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.