Antiemetics: American Society of Clinical Oncology focused guideline update

Purpose: To update a key recommendation of the American Society of Clinical Oncology antiemetic guideline. This update addresses the use of the oral combination of netupitant (a neurokinin 1 [NK1] receptor antagonist) and palonosetron (a 5-hydroxytryptamine-3 [5-HT3] receptor antagonist) for the prevention of acute and delayed nausea and vomiting in patients receiving chemotherapy. Methods: An update committee conducted a targeted systematic literature review and identified two phase III clinical trials and a randomized phase II dose-ranging study. Results: In one phase III trial, the oral combination of netupitant and palonosetron was associated with higher complete response rates (no emesis and no rescue medications) compared with palonosetron alone in patients treated with anthracycline plus cyclophosphamide chemotherapy (74% v 67% overall; P = .001). In another phase III trial, the oral combination of netupitant and palonosetron was safe and effective across multiple cycles of moderately or highly emetogenic chemotherapies. In the phase II dose-ranging study, each dose of netupitant (coadministered with palonosetron 0.50 mg) produced higher complete response rates than palonosetron alone among patients receiving cisplatin-based chemotherapy. The highest dose of netupitant (ie, 300 mg) was most effective. Recommendations: All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. The remaining recommendations from the 2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki

Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline

PURPOSE: To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options. RESULTS: A total of 41 articles met eligibility criteria and form the evidentiary basis for the guideline recommendations. RECOMMENDATIONS: Patients undergoing neoadjuvant therapy should be managed by a multidisciplinary care team. Appropriate candidates for neoadjuvant therapy include patients with inflammatory breast cancer and those in whom residual disease may prompt a change in therapy. Neoadjuvant therapy can also be used to reduce the extent of local therapy or reduce delays in initiating therapy. Although tumor histology, grade, stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) expression should routinely be used to guide clinical decisions, there is insufficient evidence to support the use of other markers or genomic profiles. Patients with triple-negative breast cancer (TNBC) who have clinically node-positive and/or at least T1c disease should be offered an anthracycline- and taxane-containing regimen; those with cT1a or cT1bN0 TNBC should not routinely be offered neoadjuvant therapy. Carboplatin may be offered to patients with TNBC to increase pathologic complete response. There is currently insufficient evidence to support adding immune checkpoint inhibitors to standard chemotherapy. In patients with hormone receptor (HR)-positive (HR-positive), HER2-negative tumors, neoadjuvant chemotherapy can be used when a treatment decision can be made without surgical information. Among postmenopausal patients with HR-positive, HER2-negative disease, hormone therapy can be used to downstage disease. Patients with node-positive or high-risk node-negative, HER2-positive disease should be offered neoadjuvant therapy in combination with anti-HER2-positive therapy. Patients with T1aN0 and T1bN0, HER2-positive disease should not be routinely offered neoadjuvant therapy.Additional information is available at www.asco.org/breast-cancer-guidelines

Antiemetics: American Society of Clinical Oncology clinical practice guideline update

Purpose: To update the ASCO guideline for antiemetics in oncology. Methods: ASCO convened an Expert Panel and conducted a systematic review of the medical literature for the period of November 2009 to June 2016. Results: Forty-one publications were included in this systematic review. A phase III randomized controlled trial demonstrated that adding olanzapine to antiemetic prophylaxis reduces the likelihood of nausea among adult patients who are treated with high emetic risk antineoplastic agents. Randomized controlled trials also support an expanded role for neurokinin 1 receptor antagonists in patients who are treated with chemotherapy. Recommendation: Key updates include the addition of olanzapine to antiemetic regimens for adults who receive high-emetic-risk antineoplastic agents or who experience breakthrough nausea and vomiting; a recommendation to administer dexamethasone on day 1 only for adults who receive anthracycline and cyclophosphamide chemotherapy; and the addition of a neurokinin 1 receptor antagonist for adults who receive carboplatin area under the curve ≥ 4 mg/mL per minute or high-dose chemotherapy, and for pediatric patients who receive high-emetic-risk antineoplastic agents. For radiation-induced nausea and vomiting, adjustments were made to anatomic regions, risk levels, and antiemetic administration schedules. Rescue therapy alone is now recommended for low-emetic-risk radiation therapy. The Expert Panel reiterated the importance of using the most effective antiemetic regimens that are appropriate for antineoplastic agents or radiotherapy being administered. Such regimens should be used with initial treatment, rather than first assessing the patient’s emetic response with less-effective treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki

Comparative assessment of clinical benefit using the ESMO-magnitude of clinical benefit scale version 1.1 and the ASCO Value Framework Net Health Benefit score

PURPOSE To better understand the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) and the ASCO Value Framework Net Health Benefit score version 2 (ASCO-NHB v2), ESMO and ASCO collaborated to evaluate the concordance between the frameworks when used to assess clinical benefit attributable to new therapies. METHODS The 102 randomized controlled trials in the noncurative setting already evaluated in the field testing of ESMO-MCBS v1.1 were scored using ASCO-NHB v2 by its developers. Measures of agreement between the frameworks were calculated and receiver operating characteristic curves used to define thresholds for the ASCO-NHB v2 corresponding to ESMO-MCBS v1.1 categories. Studies with discordant scoring were identified and evaluated to understand the reasons for discordance. RESULTS The correlation of the 102 pairs of scores for studies in the noncurative setting is estimated to be 0.68 (Spearman’s rank correlation coefficient; overall survival, 0.71; progression-free survival, 0.67). Receiver operating characteristic curves identified thresholds for ASCO-NHB v2 for facilitating comparisons with ESMO-MCBS v1.1 categories. After applying pragmatic threshold scores of 40 or less (ASCO-NHB v2) and 2 or less (ESMO-MCBS v1.1) for low benefit and 45 or greater (ASCO-NHB v2) and 4 to 5 (ESMO-MCBS v1.1) for substantial benefit, 37 discordant studies were identified. Major factors that contributed to discordance were different approaches to evaluation of relative and absolute gain for overall survival and progression-free survival, crediting tail of the curve gains, and assessing toxicity. CONCLUSION The agreement between the frameworks was higher than observed in other studies that sought to compare them. The factors that contributed to discordant scores suggest potential approaches to improve convergence between the scales. © 2018 by American Society of Clinical Oncology