Are certain metastatic colorectal cancer patients more likely to respond to aflibercept?

This study investigated which patients with colorectal cancer benefit from adding aflibercept (Zaltrap) to FOLFIRI (5-fluorouracil [Efudex], leucovorin, irinotecan [Camptosar]) as a second treatment for colorectal cancer.

About 25% of patients have metastatic colorectal cancer (colorectal cancer that has spread to distant organs) when they are diagnosed. Metastatic colorectal cancer is usually treated with chemotherapy initially. Despite initial treatment the cancer can continue to progress and second treatments can be needed.

Aflibercept is a drug approved for the treatment of metastatic colorectal cancer. It works by stopping the growth of new blood vessels in the tumor; this essentially starves the tumor and slows its growth. Previous trials have shown that adding aflibercept to chemotherapy improves patient survival time and reduces disease progression. However, it is unclear whether specific patients have a greater benefit.

This study analyzed 1226 metastatic colorectal cancer patient records to evaluate which patients benefit from aflibercept. All patients had previously received oxaliplatin (Eloxatin)-based chemotherapy before receiving either aflibercept plus FOLFIRI or only FOLFIRI. Patient characteristics examined included age, number of organs invaded and patients’ level of activity. Patient activity was scored from 0 to 5. A score of 0 indicated they were fully active. 1 indicated they had some symptoms but could still do light work. A score of 2 indicated that they had symptoms, could no longer work and spent under 50% of their day in bed.

Higher activity scores and the number of organs invaded had the biggest impact on patient survival. Patients with an activity score of 0 had a 3.6 times lower risk of death than patients with a score of 2. The risk of death was 44.6% lower in patients with cancer in only one other organ, compared to patients whose cancer had invaded more than one other organ.

Based on these results the authors identified a “better efficacy” and a “poorer efficacy” subgroup. Patients in the better efficacy group had had a slower relapse after their first chemotherapy (more than 6 months before progression). They also had an activity score of 0 and any number of organs invaded, or an activity score of 1 and less than 2 other organs invaded. Patients in the better efficacy group who received FOLFIRI plus aflibercept had a 27% better chance of survival than patients who only received FOLFIRI. They also had slower disease progression (7.2 months compared to 4.8 months for patients who only received FOLFIRI). In the poorer efficacy subgroup no benefit was seen with aflibercept.

The authors concluded that patients can be divided into better and poorer efficacy subgroups. Patients in the better efficacy subgroup may see enhanced benefits from the combination of aflibercept and FOLFIRI. They also suggest that this subgroup profile may help doctors determine which patients are likely to have survival benefits from the treatment. 

These results were based on records from a previous trial. Further research is needed to confirm the results. 

This research was funded by Sanofi and Regeneron Pharmaceuticals, the manufacturers of aflibercept.