Abstract PS9-59: Pooled efficacy analysis from two phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early-stage breast cancer
Authors: Schwartzberg Lee S , Bhat Gajanan , Restrepo Alvaro , Hlalah Osama , Mehmi Inderjit , Moon Yong Wha , Baek Seungjae , Chawla Shanta , Lebel Francois , Cobb Patrick Wayne 
Published: February 2021

Abstract
Background: Eflapegrastim (Rolontis®, Efla) represents the first novel, long-acting granulocyte-colony stimulating factor (G-CSF) to be introduced in more than 15 years. Efla consists of a recombinant human G-CSF analog conjugated to a human IgG4 Fc fragment via a polyethylene glycol linker. Preclinical, clinical, and pharmacodynamic/pharmacokinetic data have shown increased potency for Efla versus pegfilgrastim (Peg). Both independent, randomized Phase 3 studies comparing Efla and Peg for prophylaxis of chemotherapy-induced neutropenia in patients with early-stage breast cancer (ESBC) met the primary endpoint of non-inferiority in duration of severe neutropenia (SN; ANC&lt;0.5 × 109/L) (p&lt;0.001) for Efla vs Peg in all 4 treatment cycles. Additionally, one of the studies exhibited a statistically significant reduction in the relative risk of SN in Cycle 1 with Efla. Here we provide a pooled analysis across the two pivotal studies comparing Efla vs Peg for SN in various subgroups. Methods: Patients with ESBC, who were candidates for adjuvant or neoadjuvant chemotherapy, were randomized 1:1 in two open-label Phase 3 studies to fixed-dose Efla (3.6 mg G-CSF) or standard Peg (6 mg G-CSF) administered on Day 2 following TC (docetaxel/cyclophosphamide) for a total of 4 cycles. ANCs were collected daily in Cycle 1 and 5 times in Cycles 2-4. SN was evaluated between treatment groups in Cycle 1 using Fisher’s exact test at 5% level of significance and was analyzed using multivariate logistic and Cox proportional hazards regression models. Results: A total of 643 patients who received either Efla (n=314) or Peg (n=329) were included in the analysis. The two treatment groups were well balanced for demographics and baseline characteristics. The mean age was 59 years, 38% were ≥65 years old, and 54% weighed &gt;75kg. The safety profiles, including AEs and discontinuations, for Efla and Peg were comparable, and &gt;99% of all patients received full dose of TC on schedule. The majority (67%) of patients with SN experienced a 1 day duration, occurring between Days 7 and 8 after TC. Mean duration of SN for Efla was statistically lower than for Peg (0.24 vs. 0.36 days; p=0.029). The above statistical significance was maintained for Efla after adjusting for demographic and baseline characteristics, namely age, weight, enrolling geographical region, and treatment setting in a multivariate model. Similarly, the incidence of SN for Efla was statistically lower than Peg in Cycle 1 (17.5% vs 24%; relative risk reduction [RRR]=27%; p=0.043). Univariate analysis of the incidence of SN showed a significant risk reduction in favor of Efla (8.6% vs 14.1%; p=0.034) for patients weighing &gt;75kg (p=0.034). Multivariate analysis of SN showed significant odds ratio of SN for age ≥65 years and baseline ANC &gt;6 × 109/L in favor of Efla (OR=0.42 and 0.39, respectively). The incidence of SN in Cycles 2-4 was comparable between treatment groups. Also, the incidence of febrile neutropenia and neutropenic complications was similar with &lt;5% in each treatment group. No leukocytosis, splenic rupture, or anaphylaxis was reported in any patient receiving Efla or Peg. Conclusion: A pooled analysis of two, randomized Phase 3 studies evaluating Efla vs Peg, administered once-per-cycle for prophylaxis of SN, showed Efla and Peg had similar safety profiles with Efla demonstrating a statistically significant risk reduction in SN overall and in patients weighing &gt;75kg. Eflapegrastim is a novel, long-acting and potent recombinant human G-CSF which may provide an attractive option in supporting patients at risk for SN-related complications.
Citation Format: Lee S Schwartzberg, Gajanan Bhat, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Yong Wha Moon, Seungjae Baek, Shanta Chawla, Francois Lebel, Patrick Wayne Cobb. Pooled efficacy analysis from two phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early-stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-59.