PracticeUpdate: Haematology & Oncology

ASCO 2016 7

10 practice changes I will make after attending ASCO 2016 By Jeffrey J. Kirshner MD, FACP

1. Avoid neurotoxic chemotherapy in diabetic and older patients, when other options exist. Dr Hershman et al examined the SWOG database linked to Medicare claims (in the United States) and determined that age and diabetes were predictors of the development of neuropathy (Abstract 10001). 2. Recommend an exercise program for patients starting potentially neurotoxic chemotherapy treatment such as taxanes and platinum drugs. Greenlee et al presented data from the Pathways Study (Abstract 10002) demonstrating a higher incidence of taxane-induced neuropathy in breast cancer patients who were obese and had a low level of physical activity. At the same session, Dr Kleckner presented an analysis of a subset of 314 patients in the URCC CCOP/NCORP EXCAP study (Abstract 10000). Those randomised to the exercise program had a lower incidence of early neuropathy, highly significant in older patients. Although the majority of patients were women with breast cancer, there were also men, and drugs included vinca alkaloids in addition to taxanes and platinum. 3. Consider the combination of daratumumab (D), bortezomib (V), and dexamethasone (d) [DVd] as a treatment for relapsed or refractory multiple myeloma. Dr Palumbo presented the results of the European CASTOR study at the Plenary Session, which demonstrated superiority of DVd over Vd even in patients previously treaded with V (Abstract LBA4). There was a significant improvement in response rate, progression-free survival, and time to progression, and responses were brisk, which is important in these patients, many of whom are quite symptomatic. Progression-free survival and time to progression were approximately 7 to 8 months in the Vd group but have not been reached in those who were treated with D as well. 4. Offer short-course radiotherapy with temozolomide (TMZ) in selected glioblastoma multiforme patients over the age of 65. Dr Perry presented the results of a joint EORTC/NCIC study at the Plenary Session (Abstract LBA2). The addition of TMZ to radiation therapy resulted in an improvement in overall and progression- free survival, most dramatic in patients with MGMT methylated tumours. The regimen was well-tolerated, and there was an impressive improvement in 2-year survival rates. Median survival was increased from 3.9 to 5.3 months and in MGMT methylated patients from 7.7 to 13.5 months. 5. Use intermittent rather than continuous docetaxel in the treatment of metastatic prostate cancer (Abstract 5005). Although this German study, presented by Dr Cash did not complete accrual, the intermittent regimen of docetaxel (12 weeks of the drug either weekly or every 3 weeks, followed by a drug holiday until progression) appears to be noninferior to the continuous regimen. Another approach to decrease toxicity in chemotherapy-treated patients in this population is to lower the dose of cabazitaxel in the second line setting. DeBono et al presented the results of their PROSELICA study (Abstract 5008), which demonstrated that the lower dose of 20 mg/m 2 was noninferior to the standard dose of 25 mg/m2, and there was an improved overall safety profile!

6. Add capecitabine (CAP) to gemcitabine for the adjuvant treatment of resected pancreatic cancer while we await the results from ongoing studies of even more aggressive combinations. The ESPAC-4 trial results were reported by Neoptolemos et al (Abstract LBA4006), which demonstrated an improvement in median survival from 25.5 to 28 months when CAP was added to gemcitabine, with added but manageable toxicity. These were very high-risk patients. Most impressively the 5-year survival rates were increased by the addition of CAP from 16% to 29%! 7. Not use exemestane as adjuvant treatment for invasive lobular breast cancer in favour of one of the two nonsteroidal AIs, anastrozole or letrozole (Abstract 521). There are increasing data that exemestane is less effective in patients with this histology, which was confirmed by this review of the MA.27 study by Strasser-Weippl et al. Patients with invasive lobular carcinoma had improved overall survival when treated with anastrozole as opposed to exemestane (HR, 1.8; P = 0.55), consistent with the findings in the BIG 1-98 trial. 8. Use more AC/T and less TC in patients with high-risk early breast cancer , based on the ABC analysis of three randomised trials presented by Blum et al (Abstract 1000). In this initial report, the non-anthracycline regimen did NOT demonstrate noninferiority to the anthracycline regimens. TC may be noninferior for ER- positive patients, however, but for receptor-negative patients, I will use anthracyclines in most cases. 9. Continue aromatase inhibitor (AI) therapy for at least an additional 5 years in high-risk postmenopausal women with early-stage breast cancer . Many of these women have been reluctant to stop their AI at 5 years; I have generally made recommendations case by case, but mentioned that we will have data to help guide our decisions, once we had the results from the MA.17R and B42 studies. The initial results from MA17.R were presented at the Plenary Session (Abstract LBA1) by Dr Goss. In patients treated with 5 years of AI, as initial therapy or preceded by up to 5 years of tamoxifen, extended AI treatment to 10 years (as opposed to placebo) significantly improved disease-free survival. The gains were modest, and there was an increased risk of osteoporosis; so, I don’t plan on this approach in all of these women, but I will have the discussion, considering the risks and benefits, and probably recommend continuation in women at high risk of late recurrence. Data presented in Abstract 505 by Pan et al was an analysis of predictive factors for late recurrences in ER-positive patients (over 46,000 British women followed for up to 14 years), and its findings will help in advising our patients. 10. Consider the use of checkpoint inhibitors for patients with refractory cancers as there is increasing evidence of efficacy in a number of diseases, including metastatic colorectal, with high microsatellite instability (Abstract 3501; Overman et al), squamous cell anal (Abstract 3503; Morris et al), and even metastatic bladder as first-line in cisplatin-ineligible patients (Abstract LBA4500; Balar et al). I predict that these treatments will become approved in the near future and may even be available in some circumstances under compassionate use programs.

DECEMBER 2016