Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial.

BACKGROUND: The androgen receptor is a tumour suppressor in oestrogen receptor-positive breast cancer. The activity and safety of enobosarm, an oral selective androgen receptor modulator, was evaluated in women with oestrogen receptor (ER)-positive, HER2-negative, and androgen receptor (AR)-positive disease. METHODS: Women who were postmenopausal (aged ≥18 years) with previously treated ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled in a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial done at 35 cancer treatment centres in nine countries. Participants were stratified on the setting of immediately preceding endocrine therapy and the presence of bone-only metastasis and randomly assigned (1:1) to 9 mg or 18 mg oral enobosarm daily using an interactive web response system. The primary endpoint was clinical benefit rate at 24 weeks in those with centrally confirmed AR-positive disease (ie, the evaluable population). This trial is registered with ClinicalTrials.gov (NCT02463032). FINDINGS: Between Sept 10, 2015, and Nov 28, 2017, 136 (79%) of 172 patients deemed eligible were randomly assigned to 9 mg (n=72) or 18 mg (n=64) oral enobosarm daily. Of these 136 patients, 102 (75%) patients formed the evaluable population (9 mg, n=50; 18 mg, n=52). The median age was 60·5 years (IQR 52·3-69·3) in the 9 mg group and 62·5 years (54·0-69·3) in the 18 mg group. The median follow-up was 7·5 months (IQR 2·9-14·1). At 24 weeks, 16 (32%, 95% CI 20-47) of 50 in the 9 mg group and 15 (29%, 17-43) of 52 in the 18 mg group had clinical benefit. Six (8%) of 75 patients who received 9 mg and ten (16%) of 61 patients who received 18 mg had grade 3 or grade 4 drug-related adverse events, most frequently increased hepatic transaminases (three [4%] of 75 in the 9 mg group and two [3%] of 61 in the 18 mg group), hypercalcaemia (two [3%] and two [3%]), and fatigue (one [1%] and two [3%]). Four deaths (one in the 9 mg group and three in the 18 mg group) were deemed unrelated to the study drug. INTERPRETATION: Enobosarm has anti-tumour activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical benefit, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer. FUNDING: GTx.

An examination of health care utilization during the COVID-19 pandemic among women with early-stage hormone receptor-positive breast cancer.

BACKGROUND: Women undergoing treatment for breast cancer require frequent clinic visits for maintenance of therapy. With COVID-19 causing health care disruptions, it is important to learn about how this population's access to health care has changed. This study compares self-reported health care utilization and changes in factors related to health care access among women treated at a cancer center in the mid-South US before and during the pandemic. METHODS: Participants (N = 306) part of a longitudinal study to improve adjuvant endocrine therapy (AET) adherence completed pre-intervention baseline surveys about their health care utilization prior to AET initiation. Questions about the impact of COVID-19 were added after the pandemic started assessing financial loss and factors related to care. Participants were categorized into three time periods based on the survey completion date: (1) pre-COVID (December 2018 to March 2020), (2) early COVID (April 2020 - December 2020), and later COVID (January 2021 to June 2021). Negative binomial regression analyses used to compare health care utilization at different phases of the pandemic controlling for patient characteristics. RESULTS: Adjusted analyses indicated office visits declined from pre-COVID, with an adjusted average of 17.7 visits, to 12.1 visits during the early COVID period (p = 0.01) and 9.9 visits during the later COVID period (p < 0.01). Hospitalizations declined from an adjusted average 0.45 admissions during early COVID to 0.21 during later COVID, after vaccines became available (p = 0.05). Among COVID period participants, the proportion reporting changes/gaps in health insurance coverage increased from 9.5% participants during early-COVID to 14.8% in the later-COVID period (p = 0.05). The proportion reporting financial loss due to the pandemic was similar during both COVID periods (34.3% early- and 37.7% later-COVID, p = 0.72). The proportion of participants reporting delaying care or refilling prescriptions decreased from 15.2% in early-COVID to 4.9% in the later-COVID period (p = 0.04). CONCLUSION: COVID-19 caused disruptions to routine health care for women with breast cancer. Patients reported having fewer office visits at the start of the pandemic that continued to decrease even after vaccines were available. Fewer patients reported delaying in-person care as the pandemic progressed.

Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer.

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan-Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African-American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

Real-world treatment patterns and effectiveness outcomes in patients with early-stage triple-negative breast cancer.

Background: This retrospective, observational study examined real-world treatment patterns and effectiveness outcomes in 450 patients with stage II-IIIB early-stage triple-negative breast cancer treated in the community oncology setting. Methods: Kaplan-Meier methods were used to evaluate event-free survival (EFS), time to recurrence and overall survival (OS). Cox regression models were used to evaluate predictors of EFS and OS by pathological complete response (pCR) status. Results: Among patients receiving neoadjuvant systemic therapy only, pCR was a predictor of EFS and OS. Conclusion: These results highlight the unmet need for therapies that improve outcomes for patients with early-stage triple-negative breast cancer including increasing rates of pCR among patients receiving neoadjuvant therapy.

Lay abstract This study included 450 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older, diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). The study looked at the treatments received, whether those treatments worked and the response to treatment at the time of surgery. The study findings align with findings from other studies that complete response in tissue samples is associated with improved clinical outcomes. Triple-negative breast cancer remains challenging to treat, and there is a clear need for innovation in treatment options. Intervening in the early stages of triple-negative breast cancer is critical to improving outcomes.

Healthcare resource utilization and cost among patients treated for early-stage triple-negative breast cancer.

Background: This retrospective, observational study examined real-world healthcare resource utilization (HCRU) and costs in 308 patients diagnosed with early-stage (II-IIIB) triple-negative breast cancer between 1 March 2008 and 31 March 2016. Methods: HCRU and costs were evaluated for two time periods: from neoadjuvant treatment start date to surgery (Time 1) and after surgery to recurrence or death (Time 2). Results: The sample included 236 patients who received neoadjuvant treatment without subsequent adjuvant treatment (Neo) and 72 patients who received neoadjuvant treatment followed by adjuvant treatment (Neo + adj). Mean monthly HCRU events and mean monthly costs per patient were higher in Time 1 compared with Time 2 for both groups. Conclusion: These results demonstrate the economic burden of early-stage triple-negative breast cancer especially during neoadjuvant treatment phase.

Lay abstract This study included 308 patients with early-stage triple-negative breast cancer treated in the USA at community oncology practices. Patients were female, 18 years or older and diagnosed with stage II, IIIA or IIIB breast cancer between March 2008 and March 2016, and the breast cancer was determined to be triple negative (i.e., negative for estrogen receptors, progesterone receptors and excess HER2 protein). There were 236 patients who received neoadjuvant treatment without subsequent adjuvant treatment (the Neo group) and 72 patients who received neoadjuvant treatment followed by adjuvant treatment (the Neo + adj group). The study looked at healthcare resource use and costs of care during two time periods: from neoadjuvant treatment start date to surgery (Time 1) and after surgery to recurrence or death (Time 2). Average monthly healthcare resource use and average monthly costs of care per patient were higher in Time 1 compared with Time 2 for both groups. These results demonstrate the economic and resource burden of early-stage triple-negative breast cancer especially in the time from neoadjuvant treatment initiation until surgery.

Eflapegrastim, a Long-Acting Granulocyte-Colony Stimulating Factor for the Management of Chemotherapy-Induced Neutropenia: Results of a Phase III Trial.

BACKGROUND: Eflapegrastim, a novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Preclinical and phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for neutrophil counts for eflapegrastim versus pegfilgrastim. This open-label phase III trial compared the efficacy and safety of eflapegrastim with pegfilgrastim for reducing the risk of chemotherapy-induced neutropenia. MATERIALS AND METHODS: Patients with early-stage breast cancer were randomized 1:1 to fixed-dose eflapegrastim 13.2 mg (3.6 mg G-CSF) or standard pegfilgrastim (6 mg G-CSF) following standard docetaxel plus cyclophosphamide chemotherapy for 4 cycles. The primary objective was to demonstrate the noninferiority of eflapegrastim compared with pegfilgrastim in mean duration of severe neutropenia (DSN; grade 4) in cycle 1. RESULTS: Eligible patients were randomized 1:1 to study arms (eflapegrastim, n = 196; pegfilgrastim, n = 210). The incidence of cycle 1 severe neutropenia was 16% (n = 31) for eflapegrastim versus 24% (n = 51) for pegfilgrastim, reducing the relative risk by 35% (p = .034). The difference in mean cycle 1 DSN (-0.148 day) met the primary endpoint of noninferiority (p < .0001) and also showed statistical superiority for eflapegrastim (p = .013). Noninferiority was maintained for the duration of treatment (all cycles, p < .0001), and secondary efficacy endpoints and safety results were also comparable for study arms. CONCLUSION: These results demonstrate noninferiority and comparable safety for eflapegrastim at a lower G-CSF dose versus pegfilgrastim. The potential for increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study in patients at higher risk for CIN. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced neutropenia (CIN) remains a significant clinical dilemma for oncology patients who are striving to complete their prescribed chemotherapy regimen. In a randomized, phase III trial comparing eflapegrastim to pegfilgrastim in the prevention of CIN, the efficacy of eflapegrastim was noninferior to pegfilgrastim and had comparable safety. Nevertheless, the risk of CIN remains a great concern for patients undergoing chemotherapy, as the condition frequently results in chemotherapy delays, dose reductions, and treatment discontinuations.

Real-world evaluation of effectiveness and tolerance of chemotherapy for early-stage breast cancer in older women.

PURPOSE: Older patients with early-stage breast cancer (ESBC) tend to receive less aggressive treatment, have higher mortality rates, and are underrepresented in clinical trials. Outcomes, tolerance and toxicity of chemotherapy are underreported. Thus, we assessed the outcomes of chemotherapy in the real-world in a community oncology setting. METHODS: We retrospectively chart reviewed consecutive older patients (≥ 70 years) with ESBC diagnosed between January 1, 2010, and December 31, 2016, who received chemotherapy at our institution. Study outcomes were survival estimates. Logistic regression determined associations with measures of intolerance. RESULTS: Of 1296 patients, 229 received chemotherapy. Overall, 24% had early chemotherapy cessation; 18% had dose reductions; and 27% had dose delays. Severe, life threatening and lethal toxicities occurred in 38%, 1.3%, and 2.2%, respectively; constitutional toxicity (37%) was the most common. The 1- and 3-year overall survivals were 94% and 79%; 1- and 3-year breast-specific survivals were 96% and 89%, while 1- and 3-year disease-free survivals were 95% and 82%, respectively. Anthracyclines were the most poorly tolerated regimen having associations with hospital visits (OR 10.97, 95% CI 2.10-57.23) and severe toxicities (OR 5.28, 95% CI 1.27-21.89). Anti-HER2 therapies (OR 3.03, 95% CI 1.18-7.78) and poorer performance status (PS) (OR 7.48, 95% CI 1.75-31.98) were associated with severe toxicities. Older age (> 80 years) was associated with early cessation of therapy (OR 3.64, 95% CI 1.34-9.83). CONCLUSIONS: Chemotherapy can be effectively delivered to older patients with ESBC and is reasonably well tolerated. The high rate of anthracycline intolerability, poorer PS, and advanced age should be considered when tailoring treatment regimens.

Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway.

PURPOSE: Homologous recombination (HR)-deficient breast tumors may have genomic alterations that predict response to treatment with PARP inhibitors and other targeted therapies. METHODS: Comprehensive molecular profiles of 4647 breast tumors performed at Caris Life Sciences using 592-gene NGS were reviewed to identify somatic pathogenic mutations in HR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, KMT2D, MRE11, NBN, PALB2, RAD50/51/51B, and WRN, as well as 41 markers that may be associated with treatment response to targeted anticancer therapies. RESULTS: 17.9% of breast tumors had HR mutations (HR-MT, 831/4647) [ER/PR+ , HER2- 18.3%, n = 2183; TNBC 18.2%, n = 1568; ER/PR+ , HER2+ 15.6%, n = 237; ER/PR-, HER2+ 12.9%, n = 217; unknown n = 442]. Mean TMB was higher for HR-MT tumors across subtypes (9.2 mut/Mb vs 7.6 h-wild type (HR-WT), p ≤ 0.0001) and independent of microsatellite status. MSI-H/dMMR was more frequent among HR-MT tumors (2.1% HR-MT vs 0.2% HR-WT, p ≤ 0.0001), as was tumor PD-L1 overexpression (13.2% HR-MT vs 11.0% HR-WT, p = 0.08). Additional co-alterations were similar between HR-MT and HR-WT, with the exception of PIK3CA (30.3% HR-WT vs 26.4% HR-MT, p = 0.024) and AKT1 (3.7% HR-WT vs 2.1% HR-MT, p = 0.021). AR overexpression and PIK3CA mutations were more common among ER/PR+ tumors. ERBB2 mutations were seen in both HER2+ and HER2- tumors. CONCLUSIONS: HR-MT was common across breast cancer subtypes and co-occurred more frequently with markers of response to immunotherapy (MSI-H/dMMR, TMB) compared to HR-WT tumors. Mutations were identified in both HR-MT and HR-WT tumors that suggest other targets for treatment. Clinical trials combining HRD-targeted agents and immunotherapy are underway and could be enriched through comprehensive molecular profiling.

Real-world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer.

Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor-positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor-positive, human epidermal receptor 2-negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real-world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression-free survival (PFS) and overall survival (OS). Patients were classified as ET-naïve or by relapse status following adjuvant ET ("early" recurrence during or ≤12 months of completing adjuvant ET, or "late" >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan-Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8-12.3) for early relapse, 15.4 months (10.2-21.2) for late relapse, and 18.7 months (10.1-20.8) among ET-naïve patients (P = .018). Median OS was 39.8 months (25.0-55.1) for early relapse and 61.4 months (47.1-61.4) for late relapse, but was not reached (NR; 55.6-NR) for ET-naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor-positive MBC.

Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

PURPOSE: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. METHODS: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. RESULTS: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). CONCLUSIONS: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

Use of Biomarkers and Multigene Assays in Breast Cancer.

All patients with early breast cancer should be classified by subgroup through testing estrogen receptor, progesterone receptor, and HER2 status, with or without Ki-67 proliferation percentage. Genomic expression profiling aids clinical decision-making in most patients, because most are estrogen receptor-positive. The commercially available classifiers are prognostic for distant recurrence in node-negative and also node-positive patients. Patients at genomically low risk have excellent 5-year outcomes with endocrine therapy alone. Some assays also predict for benefit from adjuvant endocrine therapy and chemotherapy in node-negative and node-positive patients, but with varying levels of evidence. Genomic classifiers are also prognostic of late relapse and may predict benefit from extended adjuvant endocrine therapy.

Selective Androgen Receptor Modulator in a Patient With Hormone-Positive Metastatic Breast Cancer.

Androgen receptors (ARs) are highly coexpressed in estrogen receptor (ER)-positive breast cancers. Their role in breast tumorigenesis has been postulated, but the mechanism is not yet well-characterized. Steroidal androgens were previously used as an anticancer strategy but fell out of favor because of toxicity and the discovery of alternative therapies. Recent attempts to modulate androgen pathway signaling have focused on AR inhibitors. This report discusses a case using a well-tolerated selective AR modulator to treat a highly pretreated patient with ER-positive breast cancer, which resulted in a durable partial response.

Myeloid Growth Factors, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

Myeloid growth factors (MGFs) are given as supportive care to patients receiving myelosuppressive chemotherapy to reduce the incidence of neutropenia. This selection from the NCCN Guidelines for MGFs focuses on the evaluation of regimen- and patient-specific risk factors for the development of febrile neutropenia (FN), the prophylactic use of MGFs for the prevention of chemotherapy-induced FN, and assessing the risks and benefits of MGF use in clinical practice.

NCCN Guidelines Insights: Antiemesis, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.

NCCN Guidelines Insights: Breast Cancer, Version 1.2017.

These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred. CONCLUSIONS: First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

Effectiveness outcomes and health related quality of life impact of disease progression in patients with advanced nonsquamous NSCLC treated in real-world community oncology settings: results from a prospective medical record registry study.

BACKGROUND: Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. METHODS: Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Cox regression methods. PROs were analyzed with linear mixed model regression to examine changes over time, and the effect of disease progression. RESULTS: Of 147 patients in the study, 145 provided PRO data. Patients in treatment groups were: A (n = 66, 44.9%); B (n = 25, 17.0%); C (n = 56, 38.1%). A was associated with significantly longer OS than B (HR = 0.341, p = 0.0012), and significantly longer than C (HR = 0.602, p = 0.0354). PFS results were similar. Irrespective of regimen group and on 12/32 measures, patients showed significant and clinically meaningful worsening of symptoms and HRQOL at disease progression. After disease progression, the pattern of symptom and HRQOL change showed continued worsening. CONCLUSIONS: Bevacizumab-containing regimens were associated with longer PFS and OS compared with non-bevacizumab regimens. PRO measures show disease progression is associated with worsening HRQOL. Delaying disease progression can sustain better HRQL and reduce symptom burden.

Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy.

BACKGROUND: Rolapitant, a novel neurokinin-1 receptor antagonist, provided effective protection against chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin. METHODS: Patients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life. RESULTS: In the subgroup administered carboplatin-based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0-120 hours; 80.2% vs 64.6%; P < .001) and in the delayed phase (>24-120 hours; 82.3% vs 65.6%; P < .001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment-emergent adverse events was similar for the rolapitant and control groups. CONCLUSIONS: Rolapitant provided superior CINV protection to patients receiving carboplatin-based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin-treated patients. Cancer 2016;122:2418-2425. © 2016 American Cancer Society.