Based on evidence from the phase 3 ADVANCE and RECOVER trials, the FDA has approved eflapegrastim-xnst injection to decrease the incidence of infection related to febrile neutropenia for patients with non-myeloid malignancies who are receiving treatment with myelosuppressive anti-cancer agents known to be associated with clinically significant neutropenia.
The FDA has approved eflapegrastim-xnst (Rolvedon) injection to help decrease infection brought on by febrile neutropenia for patients with non-myeloid malignancies who are on myelosuppressive anti-cancer drugs that are associated with clinically significant neutropenia, according to a press release from Spectrum Pharmaceuticals.1
Two identically designed phase 3 trials helped lead to the approval: the phase 3 ADVANCE trial (NCT02643420) and the phase 3 RECOVER trial (NCT02953340).2,3 The ADVANCE trial aimed to investigate the efficacy and safety of eflapegrastim vs pegfilgrastim (Neulasta) to reduce the risk of chemotherapy-induced neutropenia in patients with early-stage breast cancer, while the RECOVER trial investigated the same regimen in patients with stage I to IIIA early-stage breast cancer.
Eflapegrastim is a long-acting granulocyte colony-stimulating factor. Investigators noted that the treatment is not indicated in the mobilization of peripheral blood cell progenitor cells for hematopoietic stem cell transplantation.
A total of 406 patients were enrolled and randomly assigned to either the eflapegrastim group (n = 196) or the pegfilgrastim group (n = 210). Patient characteristics were well balanced between arms.
During cycle 1, 15.8% of patients in the eflapegrastim arm had severe neutropenia vs 24.3% in the pegfilgrastim arm. Eflapegrastim resulted in an 8.5% relative risk reduction vs 34.9% in the pegfilgrastim arm (P = .034). In terms of duration of severe neutropenia in the eflapegrastim arm, 12% had toxicity lasting 1 day, 3% lasting 2 days in 3%, and 1% lasting 3 days compared with 15% lasting 1 day, 8% lasting 2 days, and 1% lasting 3 days in the pegfilgrastim arm.
The mean duration of severe neutropenia in cycle 1 was 0.20 ± 0.503 days in the eflapegrastim arm vs 0.35 ± 0.683 days in the pegfilgrastim arm, with a –0.148-day difference in the mean duration of severe neutropenia (95% CI, –0.264 to –0.032) which showed noninferiority (P <.0001). Moreover, the difference highlighted statistical significance in the eflapegrastim arm (P = .013) with a 42% reduction in the mean duration of severe neutropenia during cycle 1.
Adverse effects (AEs) were consistent with those previously reported. The most common treatment-related AE was bone pain, which occurred in 32% of patients, with 5% in the eflapegrastim arm vs less than 1% in the pegfilgrastim arm having grade 3 AEs. Treatment discontinuation due to AEs occurred in 5% of patients in both arms. Serious AEs occurred in 18% vs 14% in the eflapegrastim vs pegfilgrastim arms, respectively.
A total of 237 patients were enrolled, including 118 in the eflapegrastim arm and 119 in the pegfilgrastim arm. Patient characteristics were similar between both cohorts.
In cycle 1, severe grade 4 neutropenia occurred in 20.3% of patients in the eflapegrastim arm vs 23.5% in the pegfilgrastim arm. Duration of severe neutropenia in the eflapegrastim arm was 1 day in 11% of patients, 2 days in 8%, and 3 days in 2%. In the pegfilgrastim arm, the duration of severe neutropenia was 1 day in 17% of patients, 2 days in 3%, 3 days in 3%, 4 days in 1%, and 7 days in 1%.
In the eflapegrastim arm, the mean duration of severe neutropenia was 0.31 days vs 0.39 days in the pegfilgrastim arm. Between the 2 arms, the mean difference in the duration of severe neutropenia was –0.074 days (95% CI, –0.292 to 0.129) which met the primary end point of noninferiority (P <.0001).
Febrile neutropenia occurred in 0.8% of patients in the eflapegrastim arm vs 3.4% in the pegfilgrastim arm during cycle 1 (P = .370). Neutropenic complications occurred in 0.8% of patients in the pegfilgrastim arm vs 4.2% in the pegfilgrastim arm (P = .213). In both arms, patients received anti-infectives if complications arose.
AEs were consistent with those previously reported. The most common treatment-emergent AEs were lymphopenia, neutropenia, and nausea. The most common drug-related AE was bone pain occurring in 34% of patients in the eflapegrastim arm vs 38% in the pegfilgrastim arm, with grade 3 pain being reported in 2 patients vs 1, respectively. Grade 3 bone pain was resolved with analgesics.