Two-Drug Combo in KRAS Wild-Type CRC Worsened Quality of Life

Article

The two drug combination of cetuximab plus brivanib alaninate worsened quality of life and did not improve overall survival in patients with KRAS wild-type metastatic colorectal cancer.

Colorectal cancer patient with liver metastases

Colorectal cancer patient with liver metastases

The two-drug combination of cetuximab plus brivanib alaninate worsened quality of life and did not improve overall survival in patients with KRAS wild-type metastatic colorectal cancer, according to the results of a subanalysis of the CO.20 phase III trial.

“This study challenges the ‘more is more’ paradigm, which has evolved from efforts to cure cancer,” said study author Jolie Ringash, MD, of the department of radiation oncology at Princess Margaret Cancer Centre. “It may be that when working with patients who cannot be cured, where maintaining quality of life is the focus, the least toxic therapy which can still suppress cancer progression, may be the best approach.”

In the trial, 750 patients with KRAS wild-type metastatic colorectal cancer were randomly assigned to treatment with cetuximab plus brivanib alaninate or cetuximab plus placebo. For the quality-of-life analysis, 721 patients were assessed at baseline and weeks 2, 4, 6, 8, 12, 16 and 24, until disease progression. The primary quality-of-life endpoints were first time to deterioration on the Physical Function and Global Scales.

Results of the overall survival analysis showed no significant difference between the two treatment groups. Patients assigned the investigational drug combination had a median overall survival of 8.8 months compared with 8.1 months for patients on the single-drug regimen. Cetuzimab/brivanib was superior for progression-free survival with a statistically significant 1.6 month improvement compared with the placebo arm.

“Using the two drugs simultaneously to fight their cancers was not better than a single drug,” Ringash said. “In fact, the patients experienced an earlier deterioration in quality of life when taking the two drugs, they did not live longer, and they spent a greater part of their remaining survival with poor quality of life.”

Patients assigned cetuximab/brivanib had a significantly shorter median time to definitive deterioration compared with placebo for the physical scale (1.7 months vs 5.6 months; P < .0001) and the global scale (1.6 months vs 1.1 months; P = .02).

The researchers also looked specifically at the 6-week and 8-week time points. No significant differences were found between the two arms on the global scale at these time points, but on the physical scale the two-drug combination resulted in significantly worse deterioration at both 6 weeks (31% vs 17%) and 8 weeks (30% vs 20%).

Finally, administration of the investigational drug was associated with a higher rate of grade 3 fatigue, hypertension, rash, diarrhea, abdominal pain, dehydration, and anorexia. The researchers hypothesized “that the increased number of adverse events and reported symptoms observed with the two-drug combination could account for the more rapid deterioration” of quality-of-life outcomes.

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