ASCO 2016 Update: What Will Effect Treatment In Clinic Now CAGPO - - PowerPoint PPT Presentation

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ASCO 2016 Update: What Will Effect Treatment In Clinic Now CAGPO Conference Sept 29, 2016 Dr. Simon Yu Disclosures In compliance with accreditation, we require the following disclosures to the session audience: Research Support/P.I. N/A

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ASCO 2016 Update: What Will Effect Treatment In Clinic Now

CAGPO Conference Sept 29, 2016

  • Dr. Simon Yu
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Disclosures

Presentation includes discussion of the following off- label use of a drug or medical device: N/A Research Support/P.I. N/A Employee N/A Consultant N/A Major Stockholder N/A Speakers Bureau N/A Honoraria Roche, Novartis Scientific Advisory Board N/A

In compliance with accreditation, we require the following disclosures to the session audience:

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Discussion Topics

  • MA‐17R – Extended letrozole beyond 5 years of aromatase inhibitors

in early post‐menopausal hormone sensitive breast cancer

  • PALOMA‐2 – Letrozole +/‐ palbociclib in first line treatment of

hormone sensitive metastatic breast cancer

  • ESPAC‐4 – Adjuvant Capecitabine/Gemcitabine for resected

pancreatic adenocarcinoma

  • CRITICS – Peri‐operative chemotherapy vs chemoradiation for early

resectable stomach cancer

  • SWISH – Prophylactic oral steroid mouth rinse for patients undergoing

exemestane + everolimus treatment in metastatic breast cancer

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CCTG MA.17R <br />

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 2

Presented By Paul Goss at 2016 ASCO Annual Meeting

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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

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Slide 4

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 5

Presented By Paul Goss at 2016 ASCO Annual Meeting

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MA.17R – Hypothesis and Trial Objectives

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 4

Presented By Nancy Davidson at 2016 ASCO Annual Meeting

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Slide 7

Presented By Paul Goss at 2016 ASCO Annual Meeting

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MA.17R - Statistical Considerations

Presented By Paul Goss at 2016 ASCO Annual Meeting

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RESULTS

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Presented By Paul Goss at 2016 ASCO Annual Meeting

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Presented By Paul Goss at 2016 ASCO Annual Meeting

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

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 13

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 14

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 15

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 17

Presented By Paul Goss at 2016 ASCO Annual Meeting

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MA.17R – Quality of Life

Presented By Paul Goss at 2016 ASCO Annual Meeting

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Presented By Paul Goss at 2016 ASCO Annual Meeting

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Slide 22

Presented By Paul Goss at 2016 ASCO Annual Meeting

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How has this changed my practice?

  • For patients finishing 5 years of adjuvant AI therapy, we now have a better

informed discussion about continuing AI – can quantify degree of benefit

  • Decision based on benefit/side effect ratio: what is expected benefit of

continuing AI based on present risk of relapse? What is expected side effect profile? What is patient’s life expectancy?

  • Currently not funded by BCCA (CAP requests denied x 2 since ASCO

presentation) – private cost for 30 day supply of letrozole approx $100, anastrazole and exemestane approx $150

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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

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Background: CDK-4/6

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Slide 3

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Slide 4

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Palbociclib and Breast Cancer

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Slide 6

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Slide 7

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Demographics and Baseline Characteristics (ITT)

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Efficacy Results

Presented By Richard Finn at 2016 ASCO Annual Meeting

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

Presented By Richard Finn at 2016 ASCO Annual Meeting

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PFS: Blinded Independent Central Review<br />Confirms PFS Advantage Observed Using Investigator Assessment

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Slide 12

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Key Secondary Efficacy Endpoints

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Consistency of 1o and 2o Efficacy Endpoints Across PALOMA-1 and PALOMA-2 Studies

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Safety and Tolerability

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Treatment Administration (As-Treated Population)

Presented By Richard Finn at 2016 ASCO Annual Meeting

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TEAEs Occurring in ≥15% of Patients─All Causality <br />

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Summary of Adverse Events

Presented By Richard Finn at 2016 ASCO Annual Meeting

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Conclusions

Presented By Richard Finn at 2016 ASCO Annual Meeting

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How has this changed my practice?

  • I have had discussions with the appropriate patient regarding first line

NSAI + CDK 4/6 Inhibitor

  • Meaningful improvement in clinical efficacy with negligible toxicities
  • However, no public funding (yet) for this medication. Cost on a self‐

pay basis approximately $6200 per month – patient support program available

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Slide 1

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 2

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 3

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 4

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 5

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 6

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 7

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Eligibility

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Patient Demographics

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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On-Study Data

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Tumour Pathology

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 12

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Treatment Received

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Reported Toxicity

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Serious Adverse Events

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 16

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Survival by Treatment

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 18

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 20

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Treatment Effect by R-Status

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Slide 21

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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Conclusions

Presented By John Neoptolemos at 2016 ASCO Annual Meeting

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How has this changed my practice?

  • Adjuvant capecitabine/gemcitabine should become standard of care

for resected pancreatic adenocarcinoma

  • I have not yet seen had this discussion with any patients
  • ? Covered by BCCA CAP – If not, capecitabine at 1500mg BID 21/28

costs approximately $600 per cycle

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A Multicenter Randomized Phase III Trial of Neo-adjuvant Chemotherapy Followed by Surgery and Chemotherapy or by Surgery and Chemoradiotherapy in Resectable Gastric Cancer

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Disclosures

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Background (1)

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Background (2)

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Aim

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Trial design

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Treatment Details

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Patient Eligibility

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Trial Overview

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Baseline Patient Characteristics

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Study Profile

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Pre-operative Toxicity

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Surgery

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Surgery Related Complications

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Pathology

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Post-operative Noncompliance

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Post-operative Toxicity

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Overall Survival

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Results: Progression-Free Survival

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Summary (1)

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Summary (2)

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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Conclusions

Presented By Marcel Verheij at 2016 ASCO Annual Meeting

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How has this changed my practice?

  • Makes me glad not to be a radiation oncologist…
  • Confirms previous studies that perioperative chemotherapy is

standard of care, as it is in many parts of the world (especially Asia)

  • ARTIST study from S. Korea also showed no benefit in adding

radiation therapy to post‐op chemotherapy for resected early stomach cancer (ARTIST II study only including node+ patients pending)

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Steroid‐based Magic Mouth Washes as Prophylaxis for Everolimus‐Associated Stomatitis.

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BAC BACKGROUND

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Stomatitis is a the most frequent adverse event associated with mTOR inhibition and can impact adherence and patient quality of life

  • Among patients receiving EVE plus EXE, all‐grade stomatitis was 67%; 30% had

grade ≥2 1,2

  • More than a third of grade ≥ 2 stomatitis and related events occurred in the

first 2 weeks of initiating everolimus +exemestane (median time to onset was 15 days): the incidence of new stomatitis (grade ≥2) plateaued at 6 weeks1

  • In a recent meta‐analysis of phase 3 trials of solid tumors (BC, RCC, pNET) and

TSC, 89% of first stomatitis events occurred within 8 weeks of initiating EVE3

  • 1. Yardley DA, et al. Adv Ther. 2013;30(10):870‐884. 2. Rugo HS, et al. Ann Oncol. 2014;25(4):808‐815. 3. Rugo HS, et al. Ann Oncol.

2016;00:1‐7.

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  • 1. Jones VE et al, Evaluation of Miracle Mouthwash (MMW) Plus Hydrocortisone versus Prednisolone Mouth Wash as Prophylacxis for Everolimus-

associated stomatitis: Preliminary results of a randomized phase II study: poster presented at SanAntonio Breast Cancer Symposium, December 2015; San Antonio Tx.

PRESENTED AT SABCS 2015

†Miracle mouthwash solution contained 320 mL oral Benadryl, 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin solution, in water

‡Prednisolone oral soluon contained 15 mg prednisolone/5 mL oral soluon

*Includes preferred terms: stomatitis, canker sores oral, mouth ulceration, mucositis oral, and oral mucosal eruption.

Jones = O'Shaughnessy

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  • 1. Jones VE et al, Evaluation of Miracle Mouthwash (MMW) Plus Hydrocortisone versus Prednisolone Mouth Wash as Prophylacxis for Everolimus-

associated stomatitis: Preliminary results of a randomized phase II study: poster presented at SanAntonio Breast Cancer Symposium, December 2015; San Antonio Tx. *Includes preferred terms: stomatitis, canker sores oral, mouth ulceration, mucositis oral, and oral mucosal eruption.

Incidence When Using Prophylactic Management Incidence in BOLERO‐2 (No prophylactic Management) N patients (%) % patients ( n =485) 12/47 (26%) All grades 67% 8/47 (17%) Grade 1 34% 4/47 (9%) Grade 2 25% 0/47 (0%) Grade 3 8% 0/47 (0%) Grade 4 0%

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  • 1. Jones VE et al, Evaluation of Miracle Mouthwash (MMW) Plus Hydrocortisone versus Prednisolone Mouth Wash as Prophylacxis for Everolimus-

associated stomatitis: Preliminary results of a randomized phase II study: poster presented at SanAntonio Breast Cancer Symposium, December 2015; San Antonio Tx. *Includes preferred terms: stomatitis, canker sores oral, mouth ulceration, mucositis oral, and oral mucosal eruption.

Action taken for Grade ≥ 2 stomatitis and related events N patients (%) No action 3/47 (6%) Dose delay 1/47 (2%) Dose reduction 0/47 (0%)

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Dr

  • Dr. Rug

Rugo: St Stom

  • matitis

itis Preve Prevention st study: SWI SWISH

  • 1. 2014 ASCO, Rugo et al. TPS661 Poster, NCT # NCT02069093 ; 2. Donahue SR et al. 2015 Oncology Nurse Advisor Navigation Summit; June 26-28, 2015; Hyatt Regency, Denver, Colorado.

PRESENTED AT ASCO 2016 June 5th

1

  • Median age was 61 years (range 34‐87); 61.6% were Caucasian; 93% were classified with ECOG performance status of

0‐1

  • 20 (23%) patients received optional antifungal oral prophylaxis against oral thrush
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St Stom

  • matitis

itis Evalua aluation: tion: Evaluation done by investigator via physical exam or

phone call: Evidence of changes to oral mucosa consistent with stomatitis.

| Presentation Title | Presenter Name | Date | For Internal Use Only 98

Sarah R Donohue

Normal diet was reported in 88%

  • f patients at 8 weeks

The mean oral pain score was <1 at all visits (range 0.1‐0.6)

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99

Sarah R Donohue

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Patient Education and Instructions

  • Swish and spit 10 mL of mouthwash 4 times each day
  • Hold mouthwash in mouth for a minimum of 2 minutes
  • Swish it around in the mouth, so it comes in contact with every surface of the mouth
  • Spit it out (do not swallow mouthwash)
  • Abstain from eating or drinking for at least 1 hour after performing mouthwash regimen
  • Continue with assigned oral care regimen for the first 2 months (56 days) of everolimus +

exemestane therapy, after which mouthwash will be stopped: a,b

  • a Patients will continue to be followed up for safety for an additional 2 months (56 days).
  • b An additional 2 months (56 days) of mouthwash may be administered as per the physician’s discretion.
  • A baseline oral assessment was conducted, and patients were provided instructions on how to

self-monitor for stomatitis, along with instructions to contact the study site at the first sign of oral pain or changes to the oral mucosa

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NDS: Normalcy of Diet Scale; VAS: visual analog scale

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Re Results

  • The incidence of grade ≥2 stomatitis at 8 weeks was 2.4% (n=2, 95% CI 0.29‐8.24, P<0.001) compared with a total of 33% in

BOLERO‐2

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Incidence of Stomatitis

BOLERO‐2, The Breast Cancer Trials of Oral Everolimus‐2 BOLER‐2 stomatitis grading based on CTCAE v3.0

In the 2 patients who developed grade ≥2 stomatitis, resolution to grade ≤1 occurred after a duration of 11 days for 1 patient and 15 days for the other patient

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Secondary Outcomes

  • 95% of patients used dexamethasone mouthwash 3‐4 times/day (median 3.95 [range 1.9‐4])
  • >70% of patients remained on all 3 drugs at ≥8 weeks (eve, exe and dexamethasone)
  • The median dose intensities of EVE and EXE were 10 mg and 25 mg, respectively

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Secondary Outcomes

Outcomes Number of mouthwash applications/day, median (range) 3.95 (1.9‐4.0) Actual dose intensity, mg, (range) SWISH BOLERO‐2 Everolimus 1 0 (3‐10) 8 .6

EVE: everolimus; EXE: exemestane

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Safety Outcomes

  • No new safety signal
  • The incidence of treatment‐related SAEs was 6.5%
  • 2 patients developed oral candidiasis; both used antifungal prophylaxis
  • Among 75 patients with complete ECOG scores, 88% maintained or

improved ECOG status

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  • 1. Yardley DA, et al. Adv Ther. 2013;30(10):870‐884.

AE: adverse event; BOLERO‐2, The Breast Cancer Trials of Oral Everolimus‐2; ECOG: Eastern Cooperative Oncology Group; EVE: everolimus; EXE: exemestane; SAE: serious adverse event

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How has this changed my practice?

  • Single arm phase 2 studies can still be practice changing
  • I now prescribe prophylactic alcohol free steroid mouthwash for any

patients starting everolimus/exemestane combination

  • Should this apply to patients taking everolimus for RCC or PNET?