ASCO Review- 2015 What is new in breast cancer?

Bhuvana Ramaswamy Associate Professor

The Ohio State University

OVERVIEW • Prevention • ER Positive • HER2 Positive • Triple negative

PREVENTION

Primary Results of NRG Oncology/NSABP B-35: <br />A Clinical Trial of Anastrozole vs Tamoxifen in <br />Postmenopausal Patients with DCIS

Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

B-35: Patient Population

Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

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Presented By Richard Margolese at 2015 ASCO Annual Meeting

ESTROGEN RECEPTOR POSITIVE TUMORS

CALGB 40503 (Alliance)/CTSU 40503/NCT00601900<br /><br />Phase III Trial Evaluating the Addition of Bevacizumab to Letrozole As First-line Endocrine Therapy for Treatment of Hormone-receptor Positive (HR+)<br />Advanced Breast Cancer

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Study Design - CALGB (Alliance) 40503<br />Multicenter Randomized Phase III Trial of 1st-line Letrozole +/- Bev

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Progression-Free Survival<br />CALGB (Alliance) 40503

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Overall Survival<br /> CALGB (Alliance) 40503

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Conclusions<br />CALGB (Alliance) 40503

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Implications/Future Directions<br />CALGB (Alliance) 40503

Presented By Maura Dickler at 2015 ASCO Annual Meeting

Phase III Trials Endocrine Therapy +/- Bevacizumab (open-label)

Presented By Joseph Sparano at 2015 ASCO Annual Meeting

Abstract LBA502 <br /><br /> A Double Blind Phase 3 Trial of Fulvestrant With or Without Palbociclib in Pre- and Post-menopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer That Progressed on Prior Endocrine Therapy<br />(PALOMA3 Study)

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

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Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Palbociclib

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

PALOMA3 Study Design

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

PALOMA3 Primary Endpoint: PFS<br /> (Investigator-Assessed) ITT Population

Presented By Joseph Sparano at 2015 ASCO Annual Meeting

PALOMA-1: Randomized open-label phase II trial

Presented By Joseph Sparano at 2015 ASCO Annual Meeting

Demographics and Baseline Tumor Characteristics

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Tumor Characteristics and Prior Treatment

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Adverse Events—All Cause

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Primary Endpoint: PFS (ITT Population)

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

PFS: Central Blinded Review Audit (n=211)

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Summary of Key Secondary Efficacy Endpoints

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Conclusions

Presented By Nicholas Turner at 2015 ASCO Annual Meeting

Palbociclib in HR+/HER2– BC: Phase III Studies

Presented By Joseph Sparano at 2015 ASCO Annual Meeting

Other CDK Inhibitors in Phase III Trials in Advanced ER-Positive Breast Cancer

Presented By Joseph Sparano at 2015 ASCO Annual Meeting

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Presented By Joseph Sparano at 2015 ASCO Annual Meeting

HER POSITIVE TUMORS

L Gianni, T Pienkowski, Y-H Im, L-M Tseng, M-C Liu, A Lluch, <br />E Starosławska, J de la Haba-Rodriguez, S-A Im, JL Pedrini, B Poirier, <br />P Morandi, V Semiglazov, V Srimuninnimit, GV Bianchi, <br />V McNally, H Douthwaite, G Ross, P Valagussa

Presented By Luca Gianni at 2015 ASCO Annual Meeting

NeoSphere: Phase 2 Neoadjuvant HER2+ Study

Presented By Shanu Modi at 2015 ASCO Annual Meeting

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Presented By Shanu Modi at 2015 ASCO Annual Meeting

PFS by tpCR: all treatment arms combined, <br />ITT population

Presented By Luca Gianni at 2015 ASCO Annual Meeting

Lower pCR Rates for HR+ HER2+ BC

Presented By Shanu Modi at 2015 ASCO Annual Meeting

<br />Oral Abstract Session: <br />Breast Cancer—HER2/ER<br /><br />Substantial efficacy of 12-weeks of neoadjuvant TDM1 with or without endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer: <br />WSG-ADAPT HER2+/HR+ phase II trial<br />

Presented By Nadia Harbeck at 2015 ASCO Annual Meeting

ADAPT HER2+/HR+: <br />Neoadjuvant Phase 2 Trial

Presented By Shanu Modi at 2015 ASCO Annual Meeting

Phase III, randomized study of trastuzumab emtansine ± pertuzumab vs trastuzumab + taxane for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study

Presented By Paul Ellis at 2015 ASCO Annual Meeting

MARIANNE Study Design

Presented By Shanu Modi at 2015 ASCO Annual Meeting

MARIANNE: Progression-Free Survival

Presented By Shanu Modi at 2015 ASCO Annual Meeting

Objective Response and Duration of Response by IRF

Presented By Paul Ellis at 2015 ASCO Annual Meeting

Clinical Pathway HER2+ MBC: 2015

Presented By Shanu Modi at 2015 ASCO Annual Meeting

Neratinib after adjuvant chemotherapy and trastuzumab in HER2-positive early breast cancer: Primary analysis at 2 years of a phase 3 randomized, placebo-controlled trial (ExteNET)

Presented By Arlene Chan at 2015 ASCO Annual Meeting

Adjuvant ExteNET Study Design

Presented By Shanu Modi at 2015 ASCO Annual Meeting

HERA: OS<br />(Duration Question: 2y vs 1y)

Presented By Shanu Modi at 2015 ASCO Annual Meeting

ExteNET Trial: Invasive DFS, N=2840<br />

Presented By Shanu Modi at 2015 ASCO Annual Meeting

Is extended therapy with neratinib ready to be a new standard of care?

Presented By Shanu Modi at 2015 ASCO Annual Meeting

CONCLUSIONS: HER2+ Breast Cancer

Presented By Shanu Modi at 2015 ASCO Annual Meeting

TRIPLE NEGATIVE BREAST CANCER

Results from a Phase 2 Study of Enzalutamide, an Androgen Receptor Inhibitor, in Advanced AR+ Triple-Negative Breast Cancer (MDV3100-11)

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Enzalutamide is a Potent Inhibitor of AR Signaling

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

AR Signaling and Triple-Negative Breast Cancer

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Study Schema (MDV3100-11)

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Clinical Benefit in Evaluable and ITT Populations

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

PFS in Evaluable and ITT Populations

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

AR-Driven Biology in Patients

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Clinical Benefit According to PREDICT AR

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

A Multi-Covariate Cox-Proportional Hazards Model of PFS

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Overall Survival in TNBC Patients on Enzalutamide and According to PREDICT AR Status

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Conclusions

Presented By Tiffany Traina at 2015 ASCO Annual Meeting

Prevalence and predictors of androgen receptor (AR) and programmed death-ligand 1 (PD-L1) expression in BRCA1-associated and sporadic triple negative breast cancer (TNBC) (abstr 1005)

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Vanderbilt Subtypes of TNBC

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Background: Luminal Androgen Receptor TNBC

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Background: Luminal Androgen Receptor TNBC

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Programmed death-ligand 1 (PD-L1) in TNBC

Presented By Nadine Tung at 2015 ASCO Annual Meeting

PD-L1 in TNBC: Immune Checkpoint Inhibitors

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Methods

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Immunohistochemical Staining

Presented By Nadine Tung at 2015 ASCO Annual Meeting

Conclusions

Presented By Nadine Tung at 2015 ASCO Annual Meeting

What Else is Being Clinically Targeted?

Presented By Antoinette Tan at 2015 ASCO Annual Meeting

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Presented By Antoinette Tan at 2015 ASCO Annual Meeting

SUMMARY • PRACTICE CHANGING • EXCITING • JUST FYI

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