1047 Background: In the randomized, phase III MONALEESA-2 study (NCT01958021), first-line therapy with ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor; 600 mg/day; 3-weeks-on/1-week-off) + letrozole (LET; 2.5 mg/day) in postmenopausal women with HR+, HER2– ABC significantly prolonged progression-free survival vs placebo (PBO) + LET (hazard ratio: 0.556; p = 0.00000329; Hortobagyi GN et al. N Engl J Med 2016;375:1738–48). Here we present further safety analyses from MONALEESA-2. Methods: Adverse events (AEs) were characterized per CTCAE v4.03. Analyses of key AEs included time to first event, duration (time to AE resolution), and the rate of associated dose interruptions or reductions. Results: Safety analysis included 664 patients (pts; RIB + LET: 334; PBO + LET: 330). Neutropenia was the most common all-grade (G) and G3/4 AE in the RIB + LET arm (Table); febrile neutropenia rates were low (RIB + LET arm: 1.5%) with no associated deaths. Median time to first event for G ≥2 neutropenia in the RIB + LET arm (based on neutrophil counts) was 16 days. Other common G3/4 AEs (increased by ≥5% in the RIB + LET vs PBO + LET arm) were leukopenia (21% vs 1%), elevated alanine aminotransferase (ALT; 9% vs 1%), lymphopenia (7% vs 1%), and elevated aspartate aminotransferase (AST; 6% vs 1%). Neutropenia was the most common AE leading to dose interruptions/reductions; G3/4 neutropenia led to dose interruptions in 48% vs < 1% and reductions in 30% vs 0% of pts in the RIB + LET vs PBO + LET arm. 7.5% vs 2.1% of pts (RIB + LET vs PBO + LET) discontinued due to AEs; common AEs leading to discontinuation ( > 1% pts) were elevated ALT (5% vs < 1%), elevated AST (3% vs 1%), and vomiting (2% vs 0%). Conclusions: First-line RIB + LET had a manageable safety profile in postmenopausal women with HR+, HER2– ABC. Neutropenia was the most common AE in the RIB arm, and was transient and reversible with dose modifications. Additional AE analyses will be presented. Clinical trial information: NCT01958021. [Table: see text]

Leukopenia

Letrozole

10.1200/jco.2017.35.15_suppl.1047

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Citations (7)

Supplementary Figure S7 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer

Ángel Guerrero-Zotano Stefania Belli Christoph Zielinski Miguel Gil‐Gil Antonio Fernández‐Serra

Generation and characterization of ER+ breast cancer cell lines resistant to palbociclib alone or in combination with fulvestrant

Palbociclib

10.1158/1078-0432.22490113.v1

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Supplementary Figure S8 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer

Ángel Guerrero-Zotano Stefania Belli Christoph Zielinski Miguel Gil‐Gil Antonio Fernández‐Serra

Effects of PLK1 gene modulation on cell sensitivity to palbociclib alone or in combination with fulvestrant in ER+ breast cancer cell lines

Palbociclib

Fulvestrant

10.1158/1078-0432.22490110

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Supplementary Figure S11 from CCNE1 and PLK1 Mediate Resistance to Palbociclib in HR+/HER2− Metastatic Breast Cancer

Ángel Guerrero-Zotano Stefania Belli Christoph Zielinski Miguel Gil‐Gil Antonio Fernández‐Serra

Volasertib overcomes resistance to fulvestrant and palbociclib in PLK1-overexpressing ER+ breast cancer cells

Palbociclib

Fulvestrant

10.1158/1078-0432.22490131.v1

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Supplementary Figure S3 from Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Joan Albanell José Manuel Pérez-García Miguel Gil‐Gil Giuseppe Curigliano Manuel Ruíz-Borrego

The level of mutant and wild-type circulating DNA in baseline plasma samples by patient.

Palbociclib

10.1158/1078-0432.22489437

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Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Zhen Shi Julia Wulfkuhle Małgorzata Nowicka Rosa I. Gallagher Cristina Saura

Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Triple-negative breast cancer

Complete response

10.1158/1078-0432.22483011.v1

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Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Zhen Shi Julia Wulfkuhle Małgorzata Nowicka Rosa I. Gallagher Cristina Saura

Supplementary Figure from Functional Mapping of AKT Signaling and Biomarkers of Response from the FAIRLANE Trial of Neoadjuvant Ipatasertib plus Paclitaxel for Triple-Negative Breast Cancer

Triple-negative breast cancer

Neoadjuvant Therapy

Complete response

10.1158/1078-0432.22483014.v1

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Data from Palbociclib Rechallenge for Hormone Receptor–Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Joan Albanell José Manuel Pérez-García Miguel Gil‐Gil Giuseppe Curigliano Manuel Ruíz-Borrego

<div>AbstractPurpose:To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC).Patients and Methods:The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis.Results:Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6–53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2–27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71–282.9; P = 0.018).Conclusions:Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials.</div>

Palbociclib

Regimen

Clinical endpoint

10.1158/1078-0432.c.6532953

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Supplementary Table S1 from Baseline mutations and ctDNA dynamics as prognostic and predictive factors in ER-positive/HER2-negative metastatic breast cancer patients

Javier Pascual Miguel Gil‐Gil Paula Proszek Christoph Zielinski Alistair Reay

Supplementary Table 1. List of the 21 genes included in the breast cancer panel used for sequencing, and the targeted coding regions in each case.

HER2 negative

Baseline (sea)

10.1158/1078-0432.27033649.v1