Updated phase 2 study results of lerociclib (G1T38) combined with fulvestrant support continuous dosing without a drug holiday.
A recognized treatment for patients with hormone receptor–positive, HER2-negative advanced breast cancer has been endocrine therapy. However, endocrine resistance persists as a difficult challenge in the clinical setting. In the abstract of this presentation, Iurie Bulat, MD, Institute of Oncology, Chisinau, Moldova, and colleagues discussed how the standard of care for patients with hormone receptor–positive, HER2-negative advanced breast cancer has been recognized as CDK4/6 inhibitors prescribed in conjunction with fulvestrant. Of the 3 approved CDK4/6 inhibitors, 2 require a drug holiday caused by dose-limiting neutropenia, and the last has gastrointestinal toxicity limitations.
At the 2019 San Antonio Breast Cancer Symposium, Dr Bulat and colleagues demonstrated that the combination of lerociclib and fulvestrant had similar antitumor activity, but low rates of toxicity of the gastrointestinal system and neutropenia.
In 2020, Dr Bulat presented the latest research, which were results of the lerociclib 500 mg fulvestrant phase 1/2 assessment. In this study, up to 2 previous chemotherapies in phase 1 (dose escalation) and 1 previous chemotherapy in phase 2 (dose expansion) in the advanced setting were permitted. The intent was to evaluate the recommended dose of lerociclib when combined with fulvestrant, and to assess the dose-limiting toxicities, safety, tolerability, pharmacokinetics, and preliminary efficacy.
These findings were based on the results of early 2020 reports, at which time 110 patients were enrolled in cohorts across doses of 200 mg to 650 mg once daily and 100 mg to 250 mg twice daily. The study included 20 patients who received 150 mg twice daily for a median of 6.9 months (range, 1.7-27.8 months). In the treatment arm there was a median age of 55 years (range, 33-84 years), an Eastern Cooperative Oncology Group performance status of 0 (85%), and median of 1 line of previous anticancer therapy in the advanced setting (range, 0-5).
At the 150-mg twice-daily dose of lerociclib, grade ≥3 vomiting, diarrhea, and nausea were not reported by patients. However, treatment-related adverse events included neutropenia, leukopenia, diarrhea, and anemia, and were reported at 55%, 40%, 20%, and 20%, respectively. Lastly, reports of grade 3 neutropenia were 30% and grade 4 neutropenia were 5%.
Based on Response Evaluation Criteria in Solid Tumors version 1.1, 19 patients were evaluable for tumor response at 150 mg lerociclib administered twice daily. Thirty-two percent of patients (N = 6) had a confirmed partial response, 47% (N = 9) had stable disease, and 21% (N = 4) had progressive disease. The clinical benefit rate (complete response, partial response, and stable disease ≥24 weeks) was reported as 74% in 14 of 19 patients.
Compared with other approved CDK4/6 inhibitors used in combination with fulvestrant, lerociclib’s efficacy data are consistent with available options. Vomiting, fatigue, stomatitis, diarrhea, nausea, and alopecia were reported at low rates. Based on the low observed rates of grade 4 neutropenia, continuous lerociclib dosing without a drug holiday was supported.
Source: Bulat I, Maglakelidze M, Krastev B, et al. Lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2- advanced breast cancer patients: updated phase II results and dose selection. Ann Oncol. 2020;31(4_suppl). Abstract 334P.