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

2

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: 771–84

Pooled analysis ATLAS + aTTom:<br />Breast Cancer Mortality

Slide 5

Presented By Paul Goss at 2016 ASCO Annual Meeting

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

Presented By Paul Goss at 2016 ASCO Annual Meeting

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 8

Slide 11

Presented By Paul Goss at 2016 ASCO Annual Meeting

Presented By Paul Goss at 2016 ASCO Annual Meeting

<br />MA.17R - DFS by pre-specified subgroups<br />

Presented By Paul Goss at 2016 ASCO Annual Meeting

Presented By Paul Goss at 2016 ASCO Annual Meeting

Slide 17

Presented By Paul Goss at 2016 ASCO Annual Meeting

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

Presented By Richard Finn at 2016 ASCO Annual Meeting

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

Presented By Richard Finn at 2016 ASCO Annual Meeting

Presented By Richard Finn at 2016 ASCO Annual Meeting

Presented By Richard Finn at 2016 ASCO Annual Meeting

Slide 14

Presented By Richard Finn at 2016 ASCO Annual Meeting

Hematologic AEs ─All Causality

Presented By Richard Finn at 2016 ASCO Annual Meeting

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

Presented By Richard Finn at 2016 ASCO Annual Meeting

Consistent Clinical Benefit Seen Across PALOMA Studies

Presented By Richard Finn at 2016 ASCO Annual Meeting

Presented By Richard Finn at 2016 ASCO Annual Meeting

MONARCH 1<br />Results 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

Presented By Maura Dickler at 2016 ASCO Annual Meeting

MONARCH 1: Phase 2 Study Design

Presented By Maura Dickler at 2016 ASCO Annual Meeting

MONARCH 1: Response Summary

Presented By Maura Dickler at 2016 ASCO Annual Meeting

MONARCH 1: Treatment Duration

Presented By Maura Dickler at 2016 ASCO Annual Meeting

MONARCH 1: Most Common Adverse Events

Presented By Maura Dickler at 2016 ASCO Annual Meeting

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

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Statistical Plan for ABC Trials

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Statistical Plan for ABC Trials

Presented By Joanne Blum at 2016 ASCO Annual Meeting

ABC Trials<br />Patient Characteristics % all Patients

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Results of Interim Analysis of ABC Trials

Presented By Joanne Blum at 2016 ASCO Annual Meeting

ABC Trials: Invasive Disease Free Survival

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Forest Plot of IDFS By Stratification Variables

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Slide 17

Presented By Joanne Blum at 2016 ASCO Annual Meeting

ABC Trials: First IDFS Events (N)

Presented By Joanne Blum at 2016 ASCO Annual Meeting

ABC Trials: Overall Survival

Presented By Joanne Blum at 2016 ASCO Annual Meeting

Conclusions

Presented By Joanne Blum at 2016 ASCO Annual Meeting

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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