Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer.

BACKGROUND: In MONALEESA-2, addition of ribociclib to letrozole resulted in significantly longer progression-free survival (PFS) in postmenopausal women with HR+HER2- advanced breast cancer (ABC). RIBociclib for the treatment of advanCed breast CAncer (RIBECCA) study investigated ribociclib plus letrozole in a patient population reflecting routine clinical practice. PATIENTS AND METHODS: In this multicenter, open-label, single-arm, phase 3b study, patients with HR+HER2- ABC not amenable to curative therapy and ECOG performance status ≤ 2 received ribociclib plus letrozole (cohort A: postmenopausal women and men in first-line; cohort B: pre-/perimenopausal women in first-line [B1], patients pretreated for advanced disease [B2]). The primary endpoint was clinical benefit rate (CBR) by week 24; secondary endpoints included overall response rate (ORR), PFS, overall survival (OS), and safety. Association of patient and tumor characteristics with PFS was analyzed by multivariable Cox regression analysis. RESULTS: Overall, 487 patients were evaluable for efficacy, 502 for safety. By week 24, CBR was 60.8 % (95 % CI, 56.3-65.1), ORR was 19.3 % (95 % CI, 15.9-23.1). Median PFS was 21.8 months (95 % CI, 13.9-25.3) in first-line postmenopausal patients and 11.0 months (95 % CI, 8.2-16.4) in premenopausal and pretreated patients. Median OS was not reached. Higher baseline ECOG performance status, higher histological grade, and negative progesterone receptor status showed an unfavorable effect on PFS. Most common adverse events were neutropenia (50.0 %), nausea (42.0 %), and fatigue (39.2 %). CONCLUSION: In this broad population of patients with HR+HER2- ABC, efficacy and safety results of ribociclib plus letrozole were similar to those observed in pivotal trials.

Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) in Locally Advanced or Metastatic Breast Cancer: Prospective Cohort Study.

BACKGROUND: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin. PATIENTS AND METHODS: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety. RESULTS: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients. CONCLUSION: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.