PracticeUpdate Oncology Best of 2018

EDITOR’S PICKS 12

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer The New England Journal of Medicine Take-home message • In order to determine the value of chemotherapy in patients with midrange 21-gene breast cancer recurrence scores, this prospective trial evaluated 10,273 women with HR+/HER2−, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (HR for invasive disease recurrence, second primary cancer, or death [endocrine vs chemoendocrine therapy], 1.08; P = .26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine group and 84.3% in the chemoendocrine group) and freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local–regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). • The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P = .004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. Jeffrey Wiisanen MD

was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recur- rence, second primary cancer, or death). RESULTS Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemo- therapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemo- therapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018 Jun 03;[EPub Ahead of Print], JA Spar- " …the majority of women with ESBC can now be confidently assured of an excellent prognosis without adjuvant chemotherapy based on this genomic assay. "

Abstract BACKGROUND The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. Journal of Medicine , is a practice-chang- ing study. This NCI cooperative group trial result, a decade in the making, prospec- tively validated the ability of the Oncotype DX Recurrence Score (RS), based on a 21-gene genomic expression assay, to determine whether patients with HR+, HER2−, stage I–II early-stage breast can- cer (ESBC) benefited from chemotherapy in addition to endocrine adjuvant therapy. Over 6000 patients with an intermediate RS, defined as 11–25, were randomized to receive endocrine therapy alone or to also have chemotherapy of physician’s choice. The results conclusively showed no ben- efit with the addition of chemotherapy for patients with an RS in this range. Moreover, the risk of distant recurrence at 9 years was about only 5%. This builds on prior publication and now longer follow-up that showed patients with an RS of <10 have an excellent prognosis with endocrine ther- apy alone and would not benefit from chemotherapy. Therefore, the majority of women with ESBC can now be confidently COMMENT By Lee S. Schwartzberg MD, FACP T he TAILORx trial, presented at the ASCO plenary and simultaneously published in The New England

METHODS We performed a prospective trial involving 10,273 women with hormone-recep- tor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-nega- tive breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a mid- range recurrence score of 11 to 25 and were randomly assigned to receive either chemoendo- crine therapy or endocrine therapy alone. The trial This trial will continue to be a rich source of data on an ongoing basis as longer- term follow-up continues. For now, we have a convenient test that definitively helps oncologists and patients make an important decision in treatment for the most common women’s cancer. assured of an excellent prognosis with- out adjuvant chemotherapy based on this genomic assay. As usual, the results of the TAILORx trial raise new questions. An exploratory anal- ysis suggested benefit for the subgroup of women younger than 50 years old and with an RS of 16–25, although this was a small percentage in terms of improve- ment in distant disease-free recurrence. Was this a direct cytotoxic effect of the chemotherapy or an indirect effect from causing menopause in this population? What about the patients who had an RS of 26 or greater and received chemo: was there a differential effect of the type of chemotherapy regimen given? What is the slope of the curve for recurrence based on RS for these higher-risk patients, and do they all need chemotherapy, especially those with scores just above 25?

ano, RJ Gray, DF Makower, et al. www.practiceupdate.com/c/69142

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