By Robert Wesolowski, MD June 18, 2016

1. 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

2. Disclosures
§ Chair or Data Safety Monitoring Board for Helsinn, Inc
§ Advisory Board member for Agenus, Inc
§ Advisory Board member for Novartis (Afinitor) 2016
2

3. 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
3

4. Adjuvant Tamoxifen and Recurrence of ER(+) Breast Cancer
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Lancet 2011; 378: 771–84

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

6. Slide 5
Presented By Paul Goss at 2016 ASCO Annual Meeting

7. 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

8. 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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9. Slide 11
Presented By Paul Goss at 2016 ASCO Annual Meeting

10. Presented By Paul Goss at 2016 ASCO Annual Meeting

11. <br />MA.17R - DFS by pre-specified subgroups<br />
Presented By Paul Goss at 2016 ASCO Annual Meeting

12. Presented By Paul Goss at 2016 ASCO Annual Meeting

13. Slide 17
Presented By Paul Goss at 2016 ASCO Annual Meeting

14. 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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15. CDK 4/6 Inhibitors
15

16. Presented By Richard Finn at 2016 ASCO Annual Meeting

17. Presented By Richard Finn at 2016 ASCO Annual Meeting

18. Presented By Richard Finn at 2016 ASCO Annual Meeting

19. 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

20. Presented By Richard Finn at 2016 ASCO Annual Meeting

21. Presented By Richard Finn at 2016 ASCO Annual Meeting

22. Slide 14
Presented By Richard Finn at 2016 ASCO Annual Meeting

23. Hematologic AEs ─All Causality
Presented By Richard Finn at 2016 ASCO Annual Meeting

24. Non-hematologic AEs Occurring in ≥15% of Pts - All Causality
Presented By Richard Finn at 2016 ASCO Annual Meeting

25. Consistent Clinical Benefit Seen Across PALOMA Studies
Presented By Richard Finn at 2016 ASCO Annual Meeting

26. Presented By Richard Finn at 2016 ASCO Annual Meeting

27. 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

28. Abemaciclib is a Selective Inhibitor of CDK4 & 6
Presented By Maura Dickler at 2016 ASCO Annual Meeting

29. MONARCH 1: Phase 2 Study Design
Presented By Maura Dickler at 2016 ASCO Annual Meeting

30. MONARCH 1: Response Summary
Presented By Maura Dickler at 2016 ASCO Annual Meeting

31. MONARCH 1: Treatment Duration
Presented By Maura Dickler at 2016 ASCO Annual Meeting

32. MONARCH 1: Most Common Adverse Events
Presented By Maura Dickler at 2016 ASCO Annual Meeting

33. Adjuvant Chemotherapy
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34. US Oncology 9735 Study; 7 year follow up.
34
Jones et al. J Clin Oncol 2009; 27:1177-83

35. 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

36. Presented By Joanne Blum at 2016 ASCO Annual Meeting

37. Timeline and Accrual of ABC Trials
Presented By Joanne Blum at 2016 ASCO Annual Meeting

38. Statistical Plan for ABC Trials
Presented By Joanne Blum at 2016 ASCO Annual Meeting

39. Statistical Plan for ABC Trials
Presented By Joanne Blum at 2016 ASCO Annual Meeting

40. ABC Trials<br />Patient Characteristics % all Patients
Presented By Joanne Blum at 2016 ASCO Annual Meeting

41. Results of Interim Analysis of ABC Trials
Presented By Joanne Blum at 2016 ASCO Annual Meeting

42. ABC Trials: Invasive Disease Free Survival
Presented By Joanne Blum at 2016 ASCO Annual Meeting

43. Forest Plot of IDFS By Stratification Variables
Presented By Joanne Blum at 2016 ASCO Annual Meeting

44. Slide 17
Presented By Joanne Blum at 2016 ASCO Annual Meeting

45. ABC Trials: First IDFS Events (N)
Presented By Joanne Blum at 2016 ASCO Annual Meeting

46. ABC Trials: Overall Survival
Presented By Joanne Blum at 2016 ASCO Annual Meeting

47. Conclusions
Presented By Joanne Blum at 2016 ASCO Annual Meeting

48. 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

49. Thank You
Questions?
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