San Antonio Breast Cancer Symposium 2011: Clinical Trials Report

San Antonio Breast Cancer Symposium is one of the largest gatherings of breast cancer clinicians, scientists and those with a stake in breast cancer treatment. There are over 8,000

people attending the SABCS 2011 right now.  I am following the meeting via #SABCS hashtag and using the twitter feed (the window) of @teamoncology Naoto T. Ueno, @MaverickNY Sally Church,  @3NT Pieter Droppert, @drsteventucker Steven Tucker and others to attend and report some of the exciting developments.

CLEOPATRA Phase III Study

Positive results of HER2 targeted pertuzumab (Omnitarg, 2C4)  in the first randomized Phase III trial comparing pertuzumab, trastuzumab (Herceptin) and docetaxel combination with trastuzumab and docetaxel controls in HER2-positive metastatic breast cancer.

survival

• Dr Balsega states dual HER2 blockade, pertuzumab extends progression-free survival. Dec 08. @teamoncology Naoto T. Ueno 上野直人
• Pertuzumab and Trastuzumab combo led to an additional six months of PFS, newly diagnosed HER2+ metastatic #breastcancer. Dec 08. @teamoncology
• Two agents blocking HER2 led to an additional six months of progression-free survival ow.ly/7PE7y . Dec 07. @AACR
• CLEOPATRA Ph 3 study:PFS more than doubled for patients taking pertuzumab, Herceptin, chemo vs Herceptin and chemo-12.4 vs 6.1 mos. Dec 08. @JNCI_Now J Nat'l Cancer Inst 
• Dual HER2 blockade hailed. Pertuzumab added to trastuzumab and docetaxel cuts progression risk 38% vs placebo in same combo. Dec 08. @OncLive
• Dr Baselga states that there is a trend for overall survival difference. Dec 08.  @teamoncology

toxicity

• CLEOPATRA trial reported: pertuzumab, trastuzumab & docetaxel improves PFS with no added cardiac toxicity @NEJM bit.ly/ugXrH6 . Dec 08. @NatureRevClinOncol
• Dr Baselga stide effects were minimal with the addition of pertuzumab. Diarrhea is one of the unique side effect. Dec 08. @teamoncology
• No cardiac toxicities but more diarrhea by Pertuzumab and Trastuzumab combo. Dec 08. @NatRevClinOncol

mech

• Pertuzumab, Herceptin both bind to HER2 receptor on different regions for comprehensive blockade of HER signaling pathway. Dec 08. @JNCI
• Pertuzumab prevents HER2 and HER3 to stick together. This means HER2 will not get activated for cancer. Dec 08. @teamoncology
• Dr Baselga is a great physician scientist who has really led recent many biological agent development in breast cancer. Dec 08. @teamoncology

outlook

• Dr Baselga states CLEOPATR study is a "practice change." Dr. Carey states we need to find out who really needs this. Dec 08. @teamoncology
  Baselga says adding pertuzumab to trastuzumab plus docetaxel in HER-2 pos metastatic br cancer patients may be practice-changing. . Dec 08. @JNCI_Now

BOLERO-2 STUDY

BOLERO-2 (Breast Cancer Trials of Oral Everolimus) compared everolimus (Afinitor, RAD-001; Novartis) and exemesrane (Aromasin; Pfizer) with exemesrane alone in women with metastatic estrogen receptor (ER)-positive breast cancer.  Afinitor is a small molecule inhibitor of mTOR signaling pathway which was FDA approved earlier this year for pancreatic cancer.  Aromasin, an aromatase inhibitor, blocks synthesis of estrogens.  It is approved for the adjuvant treatment of postmenopausal women with ER-positive early breast cancer.

patients

• ER+, HER2- postmenopausal women with metastatic breast cancer

survival

• Bolero 2 design-metastatic breast cancer :exemesrane alone or exemesrane and everolimus. Dec 08. @cancermd Dr Sunil Verma
• Adding everolimus to exemestane signif improves progression-free survival in HR–positive adv #breastcancer pts. nej.md/vKlOEB .  Dec 07. @NEJM 
• Dr Hortobagyi states exemestane+Everolimus prolonges 4 months prolongation of progression, 60% reduction.  Dec 08. @teamoncology
• Everolimus/exemestane combination improved PFS to 7.4 months from 3.2 months; well-tolerated.  Dec 08. @JNCI_Now J Nat'l Cancer Inst
• BOLERO-2 is HR of 0.36. Central PFS. 11 vs 4.1 M. Big big difference. Overall survival is not mature.  Dec 08. @teamoncology
• BOLERO-2 Ph. 3 study shows everolimus and exemestane more effective than single endocrine treatment in br cancer; results in NEJM.  Dec 08. @JNCI_Now

(data analysis issues!)

• BOLERO2: PFS updated from ECCO to 11.0 vs 4.1 months in ER/PR+ mBC who have previously received AI therapy.  Dec 08. @MaverickNY Sally Church
• BOLERO2 has better PFS by central than local review (unusual). Dr Hortobaygi did not explain this diff in press conference earlier.  Dec 08. @MaverickNY Sally Church
• Unclear why hortobagyi would focus on local review data that is typically less accurate than central review.  Dec 08. @3NT Pieter Droppert

adverse events, etc.

• Dr Hortobagyi states common side effects was stomatitis (59%), rash (39%), fatigue (36%) by exemestane+Everolimus.  Dec 08. @teamoncology
• Dr Hortobagyi states exemestane+Everolimus combination decreases the bone resorption to go done. Wow. .  Dec 08. @teamoncology
• BOLERO-2 study showed exemestane plus everolimus decreased bone resorption compared with exemestane alone.  Dec 08.  @JNCI_Now

mechanism

• Exemestane blocks estrogen-signaling pathway; everolimus blocks PI3-kinase/AKT/mTOR pathway in dual attack br cancer patients. .  Dec 07.  @JNCI_Now
• everolimus an mTOR inhibitor given to ER+ HER-2neg metastatic BrCa patients are promising in BOLERO-2 study .  Dec 08.  @TomBerton Tom Berton

outlook

• Dr Hortobagyi states BOLERO-2 is a way to show that hormone resistance can overcome by targeting mTOR in ER+ breast cancer.  Dec 08.  @ teamoncology
• Dr Hortobagyi states exemestane+Everolimus is a paradigm shift in the practice of hormonal agents.  Dec 08.  @teamoncology
• BOLERO-2 shows everolimus as first agent to enhance hormonal therapy in ER+ br cancer patients; cld mark paradigm shift for treatment. .  Dec 08.  @JNCI_Now
• Baselga expects trials on everolimus in HER-2 positive metastatic br cancer patients, given promising BOLERO-2 results w ER+ women.  Dec 08.  @JNCI_Now
• Sounds like pertuzumab and Afinitor will both be submitted to the FDA for breast cancer before end of year.  Dec 08.  @eyoste ElizabethWhittington
• Unless we develop biomarkers, we will not able to afford BOLERO-2. The drug only for everolimus costs $7500/month.  Dec 08.  @teamoncology

TAMRAD study

Dr H states about TAMRAD study tamoxifen +/- everolimus. Another positive Phase II study.  Dec 08.  @teamoncology

AVEREL study

survival

• Dr Gianni discuss about AVEREL study is the first randomized trial of bevacizumab in HER2+ breast cancer.  Dec 08.  @ teamoncology
• Dr Gianni discuss about AVEREL study, Bevacizumab to Docetaxel plus Herceptin Improved PFS in HER2+ Breast Cancer.  Dec 08.  @ teamoncology
• AVEREL study shows 3M prolongation of progression in HER2+ breast cancer with Avastin added to Herceptin+Chemo.  Dec 08.  @ teamoncology

outlook, future

• Avastin without benefit as 1st line recurrent disease with increased cardiac toxicity in AVEREL study.  Dec 08.  @LJaneTn Lois J Teston MD
• outlook and future
• AVEREL shows VEGF-A may be a predictive factor for Avastin containing regimen.  Dec 08.  @ teamoncology
• Dr Gianni has no idea how AVEREL will be looked by FDA. Only PFS and Avastin.  Dec 08.  @ teamoncology
• Giannit cites ongoing BETH trial; planned global biomarker study Meridian as other bevacizumab trials to watch. Dec 08. @JNCI_Now J Nat'l Cancer Inst

SWOG0226 study

Phase III Randomized Trial of Anastrozole Versus Anastrozole and Fulvestrant as first line therapy for postmenopausal women with metastatic breast cancer


survival

• Ph. III trial shows anastrozole w fulvestrant as first-line therapy improves overall survival in postmenopausal metastatic br cancer. 7 Dec. @JNCI_Now
• Anastrazole vs A + Fulvesterant, PFS as primary endpoint. PFS 13.5m for A, 15m for A+F.  7 Dec. @drsteventucker Steven Tucker, MD
• SWOG0226 study. Anastrazole vs A + Fulvesterant, PFS as primary endpoint. PFS 13.5m for A, 15m for... fb.me/1bNCIcRr5  .  7 Dec. @teamoncology

issues

• Interesting that the benefit of anastrozole plus fulvestrant is lessened with prior tamoxifen therapy.  7 Dec @MaverickNY
• @teamoncology the data suggested to me that there is benefit in combining AI plus fulvestrant but not if had prior tamoxifen? 7 Dec MaverickNY
• Indeed. RT @MaverickNY: Interesting that the benefit of anastrozole plus fulvestrant is lessened with prior tamoxifen therapy. 7 Dec @teamoncology
• Will I give Anastrazole + Fluvestrant? Mmm tough, study negative & this study was positive and also toxic. QOL?  7 Dec. @teamoncology
• Adverse events and toxicities associated with hormonal therapies in breast cancer are no cakewalk. 7 Dec. MaverickNY Sally Church
• AI + F study is fundamentally flawed in design. Need to compare sequencing (AI then F) vs combo to get real picture.  7 Dec.  @MaverickNY Sally Church
• ... What we do not know is what is the cumulative benefit of sequencing v combo upfront . 7 Dec  @MaverickNY

 outlook, future

• Is it better to give AI followed by fluvestrant or combination? Need more studies. 7 Dec. @ teamoncology

mechanism

• ...not sure why AI + fulvestrant would show an 4.5 mon extra benefit unless it's giving more comprehensive ER shutdown?  7 Dec @MaverickNY
• ... There is a need for more mechanistic study. 7 Dec  @teamoncology

BISPHOSPHONATES

Clodronate may modestly reduce the incidence of distant #breastcancer metastases ow.ly/7SbRe .  7 Dec.  @ AACR