Practice Update: Haematology & Oncology

BREAST

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EXPERT OPINION DR KIMBERLEY BLACKWELL New data and new drugs for metastatic breast cancer: Recommendations by patient subtype

References 1. Finn RS, Martin M, Rugo HS, et al. Paper presented at: 2016 Annual Meeting of the American Society of Clinical Oncol- ogy 2016; Abstract 507. 2. MONALEESA-2 trial of Novartis’ LEE011 (ribociclib) stopped due to positive ef- ficacy results at interim analysis in HR+/ HER2- advanced breast cancer [press release]. Basel, Switzerland: Novartis; May 18, 2016. 3. Dickler MN, Tolaney SM, Rugo HS, et al. Paper presented at: 2016 Annual Meet- ing of the American Society of Clinical Oncology 2016; Abstract 510.

Dr Farzanna Haffizulla of PracticeUpdate speaks with Dr Kimberly Blackwell, Professor of Medicine and Assistant Professor of Radiation Oncology at Duke University, on what’s new in metastatic breast cancer.

Dr Haffizulla: Treatment and ER-pos- itive cancer in the advance setting, and for whom should palbociclib be considered? Dr Blackwell: Well, at least in my opinion, the near doubling in PFS when you layer palbociclib on top of endocrine therapy is really im- portant. 1 Although we have, to date, not seen a survival benefit for adding palbociclib to either fulvestrant or an aromatase inhibitor, most of us would consider a doubling in disease control, as measured by PFS, pretty important for patients. This means somewhere between a 4- to 6-month delay in needing another therapy. And I think that the side effects of palbociclib are fairly manageable; you have to watch the white counts, but, other than that, I think to dou- ble the progression-free survival on top of what you were going to give the patient anyway is meaningful. In

certainly a large enough study that, if the PFS is meaningful, we should see an overall survival benefit out of PALOMA-2. Dr Haffizulla: Where do you think the next set of advances in the adjuvant treatment of hormone receptor- positive cancers will be? Dr Blackwell: You know, that’s a tough population of patients because we do such a good job of curing them of their breast cancer that it’s hard to layer things on. So, there are three ongoing studies that I’m encourag- ing my patients to participate in. First, for BRCA-mutation carriers, we have a study randomising to a PARP inhibitor, olaparib versus control; so that would make sense. You’d finish your endocrine therapy, and you’re a BRCA carrier, maybe you would participate in that study. For other ER-positive early-stage breast cancer patients, we have two other studies. We have a study randomising everolimus in addition to antiestrogen therapy versus no everolimus; that’s a large adjuvant study. And then the third one is ac- tually evaluating palbociclib versus no palbociclib in addition to an ad- juvant endocrine regimen. These are actually three very important studies in which patients could participate. Obviously we’re not going to see the data for a couple of years, but those are the studies that I’m particularly interested in.

We are quickly getting to the point where it’s not “whether or not” someone should get a CDK inhibitor, but “which one do we use?”

Dr Haffizulla: It’s nice to have choices though, right? Dr Blackwell: Yes. Although a little confusing. Dr Haffizulla: Of course. We have to wait for some more data. And how long do you think before we see overall survival data? Dr Blackwell: Well, at this year’s ASCO, PALOMA-2 is being pre- sented, 1 and we expect to see, based on the press release, that it met its progression-free survival endpoint. Usually, once we see a PFS end- point, it’s a year or two before we see an overall survival benefit. It’s

my practice, I tend to recommend it for everyone. A recent press release indicates that the Novartis CDK inhibitor (riboci- clib), when combined with letrozole also has met its endpoint. 2 Then, at this year’s meeting, we had data about abemaciclib, which is a single agent. 3 Abemaciclib is a Lilly com- pound that’s also a CDK4/6 inhibi- tor. So, I think that we are quickly getting to the point where it’s not “whether or not” someone should get a CDK inhibitor, but “which one do we use?” It will be interesting to see how all of the studies pan out.

Dr Blackwell is the director of the Duke University

breast cancer group. She has been the principle investigator on over 40 clinical trials in

metastatic breast cancer, and the co-investigator on multiple large correlative science projects. She was the principle investigator on the pre-clinical, phase 2, and phase 3 studies that led to the approval of lapatinib for the treatment of HER2 overexpressing breast cancer.

JOURNAL SCAN Self-administered acupressure for persistent cancer-related fatigue in breast cancer survivors JAMA Oncology Take-home message • “This was a randomised, single-blinded, phase III trial designed to investigate if self-administered acupressure (relaxing or stimulating acupressure) improved fatigue, sleep, and quality of life in 288 survivors of stages 0 to III breast cancer. Both relaxing and stimulating acupressure routines were associated with significantly smaller fatigue inventory scores compared with usual care. Normal fatigue levels were achieved in 60.9% and 66.2% of stimulating and relaxing acupressure participants, respectively, compared with 31.3% of participants receiving usual care. Only relaxing acupressure resulted in significant improvements in sleep quality and overall quality of life.” • Persistent fatigue in breast cancer survivors can be alleviated by either relaxing or stimulating acupressure. Dr Jeremy C. Jones

Dr Farzanna Haffizulla

practices general internal medicine in Davie, Florida and was National President of the American Medical Women’s Association, 2014–2015.

5-Year extended adjuvant aromatase inhibition

Expert Comment It’s very refreshing and important to be conducting evidence- based research in the complementary medicine arena. These results are worth telling patients undergoing treatment and those who have recently completed acute treatment. Also important is to remind patients that, because a “treatment” doesn’t require a prescription, it doesn’t guarantee its safety, and all patients should discuss their interest in wanting to try complementary medicine therapies. It is particularly advis- able to focus on those therapies that have been studied in accurately performed evidence-based trials as this increases their credibility and an oncologist’s willingness for a patient to try them. We need to discourage patients from falling into a trap of watching commercials on TV or reading ads, the inten- tion of which may be to make money and not really provide patients the clinical care they need, rely on, and deserve. Lillie Shockney, RN, BS, MAS, who’s an expert in breast cancer treatment. Ms Shockney is Administrative Director of the Johns Hopkins Breast Center and Cancer Survivorship Programs. Abstract IMPORTANCE Fatigue is a common and debilitating late-term effect of breast cancer that is associated with poor sleep and decreased quality of life, yet therapies remain limited. Acupressure has reduced fatigue in previous small studies, but rigorous clinical trials are needed. OBJECTIVES To investigate if 6 weeks of 2 types of self-admin- istered acupressure improved fatigue, sleep, and quality of life vs usual care in breast cancer survivors and to determine if changes were sustained during a 4-week washout period. DESIGN, SETTING, AND PARTICIPANTS Phase 3 randomised, sin- gle-blind, clinical trial conducted from March 1, 2011, through October 31, 2014. Women were recruited from the Michigan Tumor Registry.

INTERVENTIONS Randomisation (1:1:1) to 6 weeks of daily self- administered relaxing acupressure, stimulating acupressure, or usual care. MAIN OUTCOMES AND MEASURES The primary outcome was change in the Brief Fatigue Inventory score from baseline to weeks 6 and 10. Secondary analyses were sleep (Pittsburgh Sleep Quality Index) and quality of life (Long-Term Quality of Life Instrument). RESULTS A total of 424 survivors of stages 0 to III breast cancer who had completed cancer treatments at least 12months previ- ously were screened, and 288 were randomised, with 270 receiving relaxing acupressure (n  =  94), stimulating acupres- sure (n = 90), or usual care (n  = 86). One woman withdrew owing to bruising at the acupoints. At week 6, the percent- ages of participants who achieved normal fatigue levels (Brief Fatigue Inventory score < 4) were 66.2% (49 of 74) in relaxing acupressure, 60.9% (42 of 70) in stimulating acupressure, and 31.3% (26 of 84) in usual care. At week 10, a total of 56.3% (40 of 71) in relaxing acupressure, 60.9% (42 of 69) in stimulating acupressure, and 30.1% (25 of 83) in usual care continued to have normal fatigue. At neither time point were the 2 acupres- sure groups significantly different. Relaxing acupressure, but not stimulating acupressure, showed significant improvements in sleep quality compared with usual care at week 6, but not at week 10. Only relaxing acupressure significantly improved quality of life vs usual care at weeks 6 and 10. CONCLUSIONS AND RELEVANCE Both acupressure arms signifi- cantly reduced persistent fatigue compared with usual care, but only relaxing acupressure had significant effects on sleep quality and quality of life. Relaxing acupressure offers a pos- sible low-cost option for managing symptoms. Investigation of 2 types of self-administered acupressure for persistent cancer-related fatigue in breast cancer survivors: a randomized clinical trial. JAMA Oncol 2016 Jul 07;[EPub Ahead of Print], SM Zick, A Sen, GK Wyatt, et al.

INTERVIEW WITH DR LEE SCHWARTZBERG

Dr Lee Schwartzberg, Medical Director at the West Clinic in Mem- phis, Tennessee, discusses results of the randomised trial MA.17R.

Implications for treatment of oestrogen receptor mutations

INTERVIEW WITH DR KIMBERLEY L BLACKWELL

Dr Kimberley Blackwell, Profes- sor of Medicine and Assistant Professor in Radiation Oncology, Duke Department of Medicine in Durham, talks about the increasing

information being presented about oestrogen recep- tor mutations.

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY