asco 2016 breast cancer review

The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

ASCO Annual Meeting 2016 Breast Cancer Robert Wesolowski, MD June 18, 2016

Disclosures Chair or Data Safety Monitoring Board for Helsinn, Inc Advisory Board member for Agenus, Inc Advisory Board member for Novartis (Afinitor) 2016

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Highlights Extending aromatase inhibitor beyond 5 years:

MA17R Study (Plenary Session) Addition of palbociclib to endocrine therapy for

untreated metastatic breast cancer: Paloma 2 Study Novel CDK 4/6 inhibitor (abemaciclib): Monarch 2

Study Role of anthracycline regimen in adjuvant

chemotherapy: ABC Trial

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Adjuvant Tamoxifen and Recurrence of ER(+) Breast Cancer

Early Breast Cancer Trialists Collaborative Group (EBCTCG) Lancet 2011; 378: 77184

Pooled analysis ATLAS + aTTom:Breast Cancer Mortality

Presented By Paul Goss at 2016 ASCO Annual Meeting

MA.17R Trial Schema and Design AI x 5 yrs - Following Prior 5 years of AI - preceded or not by Tamoxifen


MA.17R Hypothesis and Objectives Does extending AI therapy from 5 to 10 years further

improve patient outcomes? Primary Objective: Disease Free Survival (from randomization to recurrence or

development of contralateral breast cancer (CBC), whichever came first)

Secondary Objectives: Overall Survival All CBC Safety Quality of life

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MA.17R - DFS by pre-specified subgroups


Conclusion First study to show benefit of extending AI beyond 5 years

resulting in 34% reduction in disease recurrences No worsening of QOL No new toxicities Bone health remains an important risk/benefit consideration AI are readily accessible around the world

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CDK 4/6 Inhibitors

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Presented By Richard Finn at 2016 ASCO Annual Meeting

PALOMA-2: Primary Results From a Phase 3 Trial of Palbociclib Plus Letrozole Compared With Placebo Plus Letrozole in Postmenopausal Women With ER+/HER2 Advanced Breast Cancer


Hematologic AEs All Causality


Non-hematologic AEs Occurring in 15% of Pts - All Causality


Consistent Clinical Benefit Seen Across PALOMA Studies


MONARCH 1Results from a phase 2 study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for metastatic disease.

Presented By Maura Dickler at 2016 ASCO Annual Meeting

Abemaciclib is a Selective Inhibitor of CDK4 & 6


MONARCH 1: Phase 2 Study Design


MONARCH 1: Response Summary


MONARCH 1: Treatment Duration


MONARCH 1: Most Common Adverse Events


Adjuvant Chemotherapy

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US Oncology 9735 Study; 7 year follow up.

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Jones et al. J Clin Oncol 2009; 27:1177-83

Background 10 year mortality is reduced by ~30% with anthracycline and taxane

containing regimen vs. no chemotherapy. 8 year mortality is further reduced by adding a taxane to anthracyclines

(RR=0.86; 95% CI 0.79-0.93). Cardiac mortality increased by ~56% with anthracyclines (RR 1.56,

2p=0.02) Increased risk of acute leukemia with anthracycline regimens (~1/200

patients) Would TC regimen provide similar benefit to anthracycline and taxane

regimen but spare patients long therm cardiac toxicity and risk of AML?

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Lancet 2012;379:432-444

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Timeline and Accrual of ABC Trials


Statistical Plan for ABC Trials


ABC TrialsPatient Characteristics % all Patients


Results of Interim Analysis of ABC Trials


ABC Trials: Invasive Disease Free Survival


Forest Plot of IDFS By Stratification Variables


ABC Trials: First IDFS Events (N)


ABC Trials: Overall Survival


Conclusions


Rate Of Stomatitis in Everolimus Treated Patients

Bolero-2 Dexamethasone study

Number receiving Everolimus 485 92*

G1 Stomatitis 26% 17.4%

G2 Stomatitis 33% 2.4%

G3 Stomatitis 8% 0%

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10 mL of commercially available 0.5 mg/5 mL dexamethasone oral solution to swish x 2 min, and spit QID for 8 wks,

*86 patients were available for efficacy

Rugo et al. Abstract 525

Thank You Questions?

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asco 2016 breast cancer review

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