Simple antiemetic prophylaxis for breast cancer patients treated with AC chemotherapy

The inseparable duo of palonosetron and netupitant

An example of representatives of the first two groups may be the combination of palonosetron and netupitant (NEPA), which offers several advantages. It interferes with both critical pathways involved in chemotherapy-induced nausea and vomiting, acts against both acute and delayed vomiting, and is available in an oral dosage form in a fixed combination.

The efficacy and safety of NEPA have been demonstrated in randomized clinical trials in patients with solid tumors, even with repeated administration. A pilot study was also conducted in breast cancer patients treated with AC chemotherapy. In that study, the NEPA + dexamethasone combination was more effective than the palonosetron + dexamethasone combination.

NEPA vs. AC chemotherapy

Further information on the efficacy of NEPA in a population of breast cancer patients treated with AC chemotherapy was provided by a study by Italian authors published in early 2020 in the journal BMC Cancer. The aim was to determine how the effectiveness of antiemetic prophylaxis would evolve over four cycles and to explore whether it also acts against nausea and vomiting that may occur later than day 5 of the cycle.

The multicenter phase II study was conducted from May to September 2016. Participants received a standard single dose of NEPA orally and 12 mg of dexamethasone intravenously before each cycle of adjuvant chemotherapy. They were treated with AC or EC regimens (doxorubicin/epirubicin + cyclophosphamide) or FEC (5-fluorouracil, epirubicin, cyclophosphamide). The goal was to achieve a complete response (CR), defined as the absence of vomiting and the condition without the need for rescue medication for 5 days after chemotherapy administration.

More than half of women without long-term difficulties

Data from 139 patients were evaluated, with 97.8% completing all four study cycles of chemotherapy. CR in cycle 1 was achieved by 70.5% of women (90% confidence interval [CI] 64.1–76.9%). In subsequent cycles, comparable efficacy was maintained: CR was achieved by 60.4% of women in cycle 2, 56.1% in cycle 3, and 52.5% in the last cycle. Cumulatively, 53% of patients maintained CR throughout all four cycles of cancer treatment.

Prophylactic effect likely persists

Women for whom prophylaxis brought CR had a lower risk of very late episodes of nausea and vomiting (on days 6−21) compared to those who did not achieve CR. The incidence of these episodes increased during treatment (approximately 10% in cycle 1 to 20% in cycles 3 and 4). In women with CR, the only predictive factor for very late complications was the occurrence of anticipatory nausea before chemotherapy administration.

NEPA has a favorable safety profile

The antiemetic triple combination was well tolerated by patients even with repeated administration. There was no increase in the incidence of adverse events during treatment. The most common complications associated with antiemetics were fatigue (3.4% of patients) and headache (2.1%).

Conclusion

The combination of NEPA + dexamethasone proved to be effective and safe even with repeated administration in AC chemotherapy. Initial analyses also suggest that if this prophylaxis is effective for the first 5 days after the administration of cancer treatment, it is associated with a lower likelihood of further nausea or vomiting later in the same cycle.

(jam)

Source: Caputo, R., Cazzaniga, M. E., Sbrana, A. et al. Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study. BMC Cancer 2020; 20 (1): 232, doi: 10.1186/s12885-020-6707-9.