The addition of bevacizumab to standard chemotherapy during second-line treatment extended OS for patients with metastatic colorectal cancer who also received the combination during first-line treatment, according to results of a phase 3 study.
The trial was the first to evaluate the impact of continued VEGF inhibition with the addition of bevacizumab (Avastin, Genentech) to standard chemotherapy in second-line treatment for patients who also underwent the combination treatment in a first-line setting, researchers said.
Dirk Arnold, MD, director of the Hubertus Wald Tumor Center at the University Cancer Center of University Clinic Eppendorf in Hamburg, Germany, and colleagues enrolled 820 patients between February 2006 and June 2010. All patients had metastatic, inoperable colorectal cancer.
All patients had received either oxiliplatin- or irinotecan-based chemotherapy plus bevacizumab as first-line therapy and progressed within 3 months after discontinuation. After disease progression, the patients were randomized to a second round of treatment, this time with the opposite chemotherapy regimen, plus either bevacizumab (n=409) or placebo (n=411).
The primary endpoint was OS. Secondary endpoints included PFS, response rate and safety.
The patients assigned to bevacizumab in second-line treatment experienced statistically significant improvements in OS and PFS compared with the patients who received chemotherapy alone.
Median OS was 11.2 months in the bevacizumab arm vs. 9.8 months in the chemotherapy-alone arm (HR=0.81; 95% CI, 0.69-0.94; P=.0062). Median PFS was 5.7 months in the bevacizumab arm vs. 4.1 months in the chemotherapy-alone arm (HR=0.68; 95% CI, 0.59-0.78; P<.0001).
“The study confirms that the continuation of bevacizumab beyond progression while changing chemotherapy is beneficial for patients,” Arnold said during a press conference. “This clearly provides a new treatment option [in the second-line setting] for patients who have been pre-treated with a bevacizumab-combination regimen.”
The response rate was 5.4% in the bevacizumab group and 3.9% among the placebo group (P=.3113).
Patients in both arms tolerated the treatments well, the researchers said. Bevacizumab-related adverse events did not increase when continuing its use beyond progression, the researchers said.
“[The findings] provide an important new insight about the biology of advanced colorectal cancer, showing us that if the disease develops resistance to chemotherapy, it does not necessarily mean that tumors become resistant to anti-angiogenic therapy,” Arnold said in a press release.
- Arnold D. Abstract #CRA3503.
- The researchers report serving as a consultant or adviser for, as well as receiving research funding and honoraria from, Amgen, Baxter International, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Merck, Novartis, Pfizer, Roche and Sanofi.