Practice Update | Onology

CONFERENCE COVERAGE 14

Ten practice changes I will make after attending ASCO 2017 By Jeffrey J. Kirshner MD, FACP

Dr Kirshner is a partner of Hematology Oncology Associates of Central New York (HOACNY), and Director of Research and serves as the Principal Investigator of the HOACNY Community Clinical Oncology Program, East Syracuse, New York.

1. I will treat selected stage III colon cancer patients with 6 rather than 12 courses of FOLFOX adjuvant chemotherapy. As presented by Shi et al in LBA1 at the Plenary Session, IDEA, the prospective pooled analysis of six phase 3 trials investigating the duration of adjuvant therapy, demonstrated noninferiority in “lower-risk” stage 3 patients (T1–3, N1). 1 There appears to be a slight improvement in DFS in patients with more advanced stage 3 disease. As expected, the longer duration was associated with more neurotoxicity and certain T4 and N2 patients (especially those at risk for neurotoxicity) might want to consider the 6 courses, after a discussion of the risks and benefits of the longer regimen. 2. I will add abiraterone/prednisone to androgen deprivation therapy in newly diagnosed high- risk hormone-naive patients with metastatic prostate cancer. As presented by Fizazi et al in LBA3 at the Ple- nary Session, LATITUDE, the phase III, double-blind randomized trial of close to 1200 patients, clearly demonstrated an improvement in overall survival with the early initiation of abiraterone in this group of patients. 2 Toxicity was manageable. Median relapse- free survival was doubled to 33 months, and median overall survival has not been reached yet (34.7 months in the control group). This approach may replace the addition of docetaxel in this group of patients, reserving chemotherapy for patients with progressive disease. 3. I will offer patients with refractory triple-negative metastatic breast cancer (TNBC) pembroli- zumab. As presented by Adams et al in abstract 1008, Keynote-086, a phase 2 study of 170 patients with previously treated TNBC, demonstrated only a 5% response rate; however, 21% of patients had sta- ble disease, averaging 6 months, with some patients without progression at over 10 months. 3 In the same study, another cohort of patients was treated with pem- brolizumab as first-line treatment for metastatic TNBC (Abstract 1088). 4 Early results of the first 52 patients demonstrate a response rate of 23%, with stable dis- ease in 17%. Follow-up is short, but the estimated 6-month PFS is 29%. Note that, currently, pembroli- zumab is not FDA-approved for this indication but can often be obtained on compassionate release, and I look forward to approval within the year. 4. I will discuss with very high-risk patients who have resected HER2-positive stage 2 and 3 breast cancer the addition of pertuzumab to tras- tuzumab in the adjuvant setting for up to 1 year. As presented by von Minckwitz et al in abstract LBA500, the randomized placebo-controlled APHINITY trial

of over 4800 patients demonstrated that the addi- tion of pertuzumab to trastuzumab improved invasive disease-free survival by a little over 1%, which was sta- tistically significant. 5 Patients with nodal involvement, particularly those with hormone receptor-negative dis- ease achieved the most benefit and merit a discussion of the risk/benefit and cost of adding pertuzumab to trastuzumab. 5. I will offer patients with refractory upper gastroin- testinal adenocarcinomas checkpoint inhibitors . Two abstracts were presented at the Oral Session which confirm the activity seen in earlier studies. Fuchs et al reported the results of KEYNOTE-059 (abstract 4003), a global study of 259 heavily pretreated patients with gastric and gastroesophageal junction cancer. 6 Overall response rate was 11.2%, with 17% stable dis- ease. Median duration of follow-up is only 5.4 months; but, so far, median duration of response is 8.1 months, with some patients still responding at over 15 months. Responses correlated with less prior treatment, with PDL-1 positivity, and, especially, with MSI status. Jan- jigian et al reported updated results of CheckMate 032 (abstract 4014), a global study of 160 similar patients who were treated with one of three nivolumab reg- imens (two in combination with ipilimumab). 7 Overall response rate was 12% with nivolumab alone but increased to 24% when combined with ipilimumab at 3 mg/kg every 3 weeks (nivolumab was decreased to 1 mg/kg every 3 weeks). Median survival has not

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