PracticeUpdate Oncology Best of 2018

CONFERENCE COVERAGE 26

10 Practice Changes By Jeffrey J. Kirshner MD, FACP

That I Will Make After Attending ASCO 2018

1 I will not add adjuvant chemotherapy to hormo- nal therapy in most node-negative ER+ patients with intermediate recurrence scores (11–25) on Oncotype Dx. The TAILORx trial results in this population of patients with primary tumors up to 5 cm were reported in by Sparano et al. 1 Treatment with hormonal therapy alone was statistically noninferior to treatment with chemotherapy plus hormonal ther- apy in terms of invasive disease-free survival (primary endpoint) as well as overall survival. A few caveats, however: Most of the patients had T1 tumors and other low-risk clinical factors, and an unplanned explora- tory analysis revealed that patients younger than 50 years appear to benefit from chemotherapy, especially if the recurrence score exceeded 20, with about a 6% absolute increase in disease-free survival. Obviously, this will need to be discussed with such patients, and shared decision-making is essential. 2 I will add capecitabine to temozolomide for many patients with advanced pancre- atic neuroendocrine tumors who require chemotherapy. The ECOG-ACRIN study E2211 of 144 patients presented by Kunz et al demonstrated that patients randomized to the doublet rather than single-agent temozolomide had a significant improve- ment in progression-free survival (22.7 vs. 14.4 months) and overall survival (not reached vs. 38.0 months). 2 Interestingly, the overall response rate was no different with the addition of capecitabine, casting some doubt on the validity of the data; so, we wait for longer fol- low-up to be certain of the results. 3 I will consider shortening the duration of adjuvant trastuzumab from 12 to 6 months, especially in lower-risk patients, based on the report of PERSEPHONE. 3 Earl et al reported 4-year disease-free survival results of this randomized noninferiority study of over 4000 patients, which did indeed demonstrate that 6 months was sta- tistically noninferior to 12 months (4-year disease-free survival, 89.4% vs. 89.8%). The 12-month regimen

may have been more effective in receptor-negative patients. Caveats to keep in mind include the fact that the chemotherapy regimens in this study were gener- ally more intensive than what we are using today, and these patients did not receive neoadjuvant treatment or pertuzumab, which is often done in present times. 4 I will consider adjuvant FOLFOX rather than FL for stage II/III rectal cancer patients who had preoperative chemotherapy plus radiotherapy and surgery and residual dis- ease. Hong et al reported the long-term results of the ADORE study. 4 There was no difference in 6-year over- all survival in the entire population of 321 randomized patients, but the subset with ypN2 and minimally regressed tumors benefited from the addition of oxalip- latin in terms of improvement in disease-free survival. Those patients with complete pathologic response may not need oxaliplatin. 5 I will offer adjuvant denosumab as an option for additional adjuvant therapy in HR+ post- menopausal women receiving an aromatase inhibitor. Gnant et al reported the results of ABCSG-18, which randomized 3425 patients to denosumab versus placebo in addition to endocrine therapy. 5 Those receiving denosumab every 6 months had an improvement in 5-year disease-free survival (89.2% vs. 87.3%) and in 8-year disease-free survival (80.6% vs. 77.5%). Previous reports have demon- strated a dramatic decrease in fractures in those patients receiving the study drug. Interestingly, in a higher-risk population of early breast cancer patients (D-CARE), Coleman et al found that there was no dif- ference between those receiving denosumab versus placebo, despite a more intensive regimen (monthly x 6, then every 3 months up to 5 years). 6 Over 95% of the patients in this latter study received anthracycline and/or taxane. We now have another option to zole- dronic acid, not necessarily better, to add to adjuvant aromatase inhibitors for postmenopausal breast can- cer patients.

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