Sequential Bevacizumab Plus Chemotherapy May Not Improve Response Rates in Metastatic CRC

Colorectal cancer patient
Investigators assessed the efficacy of sequential scheduling of bevacizumab in combination with chemotherapy to improve outcomes in patients with metastatic colorectal cancer.

For patients with metastatic colorectal cancer (mCRC), the sequential administration of bevacizumab in combination with chemotherapy does not improve objective response rate (ORR); however, the combination might provide an overall survival advantage, fewer adverse events, and better health-related quality of life, according to study results published in JAMA Network Open.

Although bevacizumab is currently the standard of care in combination treatments for mCRC, results are limited regarding its clinical benefits. A team of investigators in Italy conducted an open-label, randomized, phase 3 clinical trial (ClincalTrials.gov Identifier: NCT01718873) to assess the efficacy of sequential scheduling of bevacizumab in combination with chemotherapy to improve outcomes in patients with mCRC.

The main end point was the ORR, which was measured using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points were progression-free survival, overall survival, safety, and quality of life.

A total of 230 adults (median age, 62.3 years; 59.1% men) with unresectable, previously untreated, or single line-treated mCRC were randomly assigned to receive 12 biweekly cycles of standard oxaliplatin-based regimens (modified FOLFOX-6 [levo–folinic acid, fluorouracil, and oxaliplatin]/modified CAPOX [capecitabine and oxaliplatin]) plus bevacizumab, which was either administered on the same day as chemotherapy (standard arm; n=115) or 4 days prior to chemotherapy (experimental arm; n=115).

The duration of follow-up was a median of 68.3 months. Between the 2 arms, no differences in ORR (P =.89) or progression-free survival (P =.15) were observed. Conversely, the median overall survival in the experimental arm was higher than in the standard arm (29.8 months vs 24.1 months, respectively; P =.04). In addition, the experimental arm was associated with a significant reduction in severe diarrhea (P =.006) and nausea (P =.05) as well as improvement in physical functioning (P =.02) and constipation scores (P =.003), compared with the standard arm.

As far as limitations, investigators note that the choice of ORR as a primary endpoint may not have been adequate. Additionally, due to the small sample size, researchers acknowledge they may not have been able to balance unmeasurable differences in patient outcomes via randomization with confidence.

“The results of this randomized clinical trial failed to show an improvement of the primary end point ORR from the sequential administration of bevacizumab in combination with standard oxaliplatin-based regimens in unselected patients with RAS mutations and mCRC,” the investigators noted. “However, although hypothesis generating, the [overall survival] advantage, fewer adverse effects, and better health-related [quality of life] observed in the sequential scheduling of bevacizumab administration compared with concomitant administration warrant consideration for additional clinical studies. Indeed, sequential bevacizumab administration plus chemotherapy might be relevant to optimize therapeutic efficacy and to explore antiangiogenic combination treatments with an innovative perspective,” concluded the researchers.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Avallone A, Piccirillo MC, Nasti G, et al. Effect of bevacizumab in combination with standard oxaliplatin-based regimens in patients with metastatic colorectal cancer: a randomized clinical trial. JAMA Netw Open. 2021;4(7):e2118475. doi:10.1001/jamanetworkopen.2021.18475