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Metastatic Breast Cancer

Metastatic Breast Cancer. Dr. Christine Simmons, MD MSc FRCP(C) Medical Oncologist, St. Michael ’ s Hospital Assistant Professor, University of Toronto simmonsch@smh.ca Christine.simmons@womenincancer.org. Objectives. What do medonc residents need to know about management of MBC

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Metastatic Breast Cancer

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  1. Metastatic Breast Cancer Dr. Christine Simmons, MD MSc FRCP(C) Medical Oncologist, St. Michael’s Hospital Assistant Professor, University of Toronto simmonsch@smh.ca Christine.simmons@womenincancer.org

  2. Objectives • What do medonc residents need to know about management of MBC • For clinical practice? • For exams? • What follows is my meagre attempt at both!

  3. The facts on Breast Cancer • Most common cancer among Canadian women • 1 in 9 Canadian women will develop breast cancer in their lifetime • In 2011, over 23,000 Canadian women will be diagnosed with breast cancer • A woman diagnosed with early stage breast cancer today has about an 85% chance of being alive and disease free in 5 years

  4. But… • Breast cancer is the second leading cause of cancer related deaths in Canadian women • Second only to lung cancer • Metastatic breast cancer can be devastating diagnosis for pts

  5. Diagnosing Metastatic Breast Cancer • Breast cancer pts at highest risk for development of mets within first 2 years of diagnosis • Trend continues within first 5 years

  6. …it changes perspectives…

  7. …it changes perspectives…

  8. Risk depends on: • Severity of disease • Intial T, N status • Receptor status • Triple negative pts – ironically do better if no recurrence by 2-3 years

  9. ….there is hope • Metastatic breast cancer can be controlled • Patients are living longer WITH breast cancer • Treatments have improved SURVIVAL and QUALITY OF LIFE in this population • Median survival of patient with metastatic breast cancer 2-3 years

  10. Metastatic Breast Cancer Aggressive and treatment resistant Indolent and slow growing

  11. As an example… • Patient X • 63 yo woman • Diagnosed with breast cancer in 2002 and was treated at that time to prevent recurrence • Recurred in 2006 • Bone and liver • Started treatment and did well • Cancer progressed further to lungs in 2009 • Has been on treatment with good response since • Currently her disease is stable • Between treatments she travels the world

  12. On the other end of the spectrum… • Patient Y • 49 yo woman • Diagnosed in 2008 with breast cancer, received treatment • “triple negative” • Recurred in 2009 in the chest wall and bone • Disease progressed through 4 different types of chemotherapy, did not respond to any treatment • Passed away August 2010.

  13. Most common scenario • 65 yo woman treated for a T2N2 tumour 2 years ago presents with increasing back pain in T10 area x 6 weeks • What do you do?

  14. Most common scenario • 65 yo woman treated for a T2N2 ER+PR-Her2-tumour 2 years ago presents with increasing back pain in T10 area x 6 weeks • History: as above, fatigue associated, generally not feeling well • Physical exam: tenderness over T10

  15. Metastatic Breast Cancer • Bone scan: • Lesion at T10 and in lumbar spine • How common is this kind of presentation?

  16. Metastatic Breast cancer • 70% of patient with MBC will have bone involvement at some point in course of their disease • Most common site of first metastases • Other common sites: • Liver, lung, chest wall, brain

  17. Why treat? • MBC patients have a prognosis that overall is quite good due to multitude of treatment options • Average survival after diagnosis of mets is 18-24 months • Likely better with current therapies

  18. Which medicine to offer? • Treatment options are based on many factors, including the features of the patients cancer • Sensitivity to estrogen and progesterone • Her2 status • These factors may change with time…

  19. Cancer can change too!

  20. HER2 receptor status Factors Influencing Treatment Choice in Metastatic Breast Cancer Patient preferences (e.g. oral vs. iv treatment) Prior therapy Choice of treatment Pace of disease Performance status ER/PR receptor status

  21. Treatment approach • Goals of care: • Quality of life AND quantity of life • Identify available options • Clinical Trial • Comet clinical trials consortium • www.clinicaltrials.gov • Options based on • Severity of disease • Pathological features of disease

  22. Current therapeutic options for MBC Anti-estrogen therapy Chemotherapy More toxic but response is usually faster Be aware of funding regulations at your centre! Be aware of changes in evidence Consider overall “cost” to your pt • For any pt with hormone sensitive disease • Best in strongly hormone sensitive • Takes longer to elucidate response overall* • Great option in pts with bone only disease

  23. Anti-estrogen therapies • Tamoxifen • Aromatase Inhibitor • Letrozole (Femara) • Anastrozole (Arimidex) • Exemestane (Aromasin) • Fulvestrant • Cheap • Remember LU codes! • More $$, may be available in clinical trial

  24. But is hormone therapy good enough?

  25. Approach to Chemotherapy for MBC • CCO funding regulations • ONE line of chemotherapy is funded, beyond first line it is the institution that picks up the tab! • Each institution will vary in what is feasible to fund depending on global budget • Not uncommon for breast ca pts to still be well after multiple lines of chemo

  26. Generally…. • Most patients receive an anthracycline and taxane adjuvantly • Depending on DFI may consider re-challenge with Taxane • Paclitaxel • Nab-paclitaxel (funded only if pt doesn’t tolerate the Paclitaxel) • Goal is QUALITY of life • Generally offer single agent over combination therapy • Capecitabine + Taxotere example

  27. Beyond first line…. • Evidence for response to: • Xeloda (oral) • AC • Single agent adriamycin weekly • Taxotere • Vinorelbine • Gemcitabine • CMF (IV or oral) • Gem-Cisplatin (triple negatives)

  28. Does treatment make a difference? • “Why bother with treatment if I can’t be cured? My life is over!” • “Why take treatment again, it didn’t work the first time!” • “With all the attention in the media, why haven’t you cured this yet?” • “Don’t make me take chemo again, I can’t handle it!” • “What is going to happen to me?” • “How long am I going to live?”

  29. Impact of New Agents on Survival over time • Access to new therapeutic agents for metastatic breast cancer have significantly improved patient’s survival over time Chia SK et al. Cancer 2007;110:973-9.

  30. BUT can we do better than just plain old chemo? • What about fancy targeted agents?

  31. AVADO: double-blind, placebo-controlled trial All patientsgiven optionto receive bevacizumabwith second-linechemotherapy Treat withplacebo to PD or unblind Possible open-label bevacizumab to PD after unblind • Previously untreatedLR or mBC • (N=736) • Stratification factors • Region • Prior taxane/time to relapse since adjuvant chemotherapy • Measurable disease • Hormone receptor status • Primary endpoint: PFS • Secondary endpoints: ORR, 1-year survival, OS, TTF, duration of response, quality of life, safety Docetaxel* + placebo q3w x9 Docetaxel* + bevacizumab7.5mg/kg q3w x9 Treat withbevacizumab to PD Docetaxel* + bevacizumab15mg/kg q3w x9 Miles DW, et al. ASCO 2008 *Docetaxel: 100mg/m2 q3w

  32. Placebo + docetaxel (n=241) Unstratified HR=0.86 (0.72–1.04), p=0.1163* Stratified HR‡=0.80 (0.65–1.00), p=0.0450* 9.0 8.2 8.1 AVADO: updated PFS 7.5mg dose 1.0 0.8 0.6 0.4 0.2 0 Bevacizumab 7.5mg/kg q3w + docetaxel (n=248) PFS estimate 0 6 12 18 24 30 36 Time (months) Intent-to-treat analysis; *p values are of exploratory nature Miles DW, et al. SABCS 2009. ‡censored for non-protocol therapy prior to progressive disease

  33. Placebo + docetaxel (n=241) Bevacizumab 15mg/kg q3w + docetaxel (n=247) AVADO: updated PFS 15mg dose 1.0 0.8 0.6 0.4 0.2 0 Unstratified HR=0.77 (0.64–0.93), p=0.0061* 10.1 Stratified HR‡=0.67 (0.54–0.83), p=0.0002* PFS estimate 10.0 8.2 8.1 0 6 12 18 24 30 36 Time (months) Intent-to-treat analysis; *p values are of exploratory nature Miles DW, et al. SABCS 2009. ‡censored for non-protocol therapy prior to progressive disease

  34. Placebo + docetaxel (n=241) Bevacizumab 15mg/kg q3w + docetaxel (n=247) AVADO OS: median follow-up 25 months Bevacizumab 7.5mg/kg q3w + docetaxel (n=248) 1.0 0.8 0.6 0.4 0.2 0 HR=1.03 (0.79–1.33), p=0.8528* HR=1.05 (0.81–1.36), p=0.7198* 31.9 OS estimate 30.8 30.2 0 6 12 18 24 30 36 Months Miles DW, et al. SABCS 2009. Unstratified analysis; *p values are of exploratory nature

  35. Docetaxel + bevacizumab7.5mg/kg q3wn=248 Docetaxel + bevacizumab15mg/kg q3wn=247 Second-line therapyn=175 Second-line therapyn=172 Without bevn=99 With bevn=76 Without bevn=119 With bevn=53 AVADO: patients were permitted to receive bevacizumab with second-line therapy Previously untreated LR or mBC N=736 Docetaxel + placeboq3wn=241 Open-label bevacizumabto PD after unblindn=14 Second-line therapyn=170 Without bevn=80 With bevn=90 Miles DW, et al. SABCS 2009.

  36. AVADO: Bevacizumab + Docetaxel in First-line Treatment of Advanced Breast Cancer 1. Miles DW, et al. SABCS 2009. Abstract 41. 2. Miles D, et al. ASCO 2008. Abstract LBA1011. • Adding bevacizumab to docetaxel in first-line treatment of advanced breast cancer improves PFS but not OS[1] • Previous analysis: addition of bevacizumab to docetaxel significantly improved PFS in locally recurrent or metastatic breast cancer with both 7.5-mg/kg and 15.0-mg/kg doses[2] • Updated results confirmed preliminary findings: addition of bevacizumab 15 mg/kg to docetaxel • Significantly increased ORR • Prolonged PFS • Toxicity profile similar among treatment arms

  37. RIBBON-2: Phase III Trial of Second-Line Bevacizumab + Chemotherapy in MBC Bevacizumab 15 mg/kg every 3 wks or 10 mg/kg every 2 wks† + Chemotherapy (n = 459) Patients with previously treated MBC (HER2 negative or HER2 status unknown) (N = 684) Chemotherapy Regimens*Taxane orGemcitabine orCapecitabine orVinorelbine Treat until disease progression Stratified by chemotherapy regimen, time between MBC diagnosis and first PD, and hormone receptor status; randomized 2:1 Placebo + Chemotherapy (n = 225) *Dose and schedule of chemotherapy regimens (selected by investigator): Taxane: paclitaxel 90 mg/m2/wk for 3 of 4 wks; paclitaxel 175 mg/m2, nab-paclitaxel 260 mg/m2, or docetaxel 75-100 mg/m2 every 3 wks. Gemcitabine 1250 mg/m2 on Days 1 and 8 every 3 wks. Capecitabine 2000 mg/m2 on Days 1-14 every 3 wks. Vinorelbine 30 mg/m2/wk every 3 wks. †Dose of bevacizumab dependent on chemotherapy regimen used. Brufsky A, et al. SABCS 2009. Abstract 42.

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