Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.

Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: ERRB2 (formerly HER2)-positive advanced breast cancer (ABC) remains typically incurable with optimal treatment undefined in later lines of therapy. The chimeric antibody margetuximab shares ERBB2 specificity with trastuzumab but incorporates an engineered Fc region to increase immune activation. OBJECTIVE: To compare the clinical efficacy of margetuximab vs trastuzumab, each with chemotherapy, in patients with pretreated ERBB2-positive ABC. DESIGN, SETTING, AND PARTICIPANTS: The SOPHIA phase 3 randomized open-label trial of margetuximab plus chemotherapy vs trastuzumab plus chemotherapy enrolled 536 patients from August 26, 2015, to October 10, 2018, at 166 sites in 17 countries. Eligible patients had disease progression on 2 or more prior anti-ERBB2 therapies and 1 to 3 lines of therapy for metastatic disease. Data were analyzed from February 2019 to October 2019. INTERVENTIONS: Investigators selected chemotherapy before 1:1 randomization to margetuximab, 15 mg/kg, or trastuzumab, 6 mg/kg (loading dose, 8 mg/kg), each in 3-week cycles. Stratification factors were metastatic sites (≤2, >2), lines of therapy (≤2, >2), and chemotherapy choice. MAIN OUTCOMES AND MEASURES: Sequential primary end points were progression-free survival (PFS) by central blinded analysis and overall survival (OS). All α was allocated to PFS, followed by OS. Secondary end points were investigator-assessed PFS and objective response rate by central blinded analysis. RESULTS: A total of 536 patients were randomized to receive margetuximab (n = 266) or trastuzumab (n = 270). The median age was 56 (27-86) years; 266 (100%) women were in the margetuximab group, while 267 (98.9%) women were in the trastuzumab group. Groups were balanced. All but 1 patient had received prior pertuzumab, and 489 (91.2%) had received prior ado-trastuzumab emtansine. Margetuximab improved primary PFS over trastuzumab with 24% relative risk reduction (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P = .03; median, 5.8 [95% CI, 5.5-7.0] months vs 4.9 [95% CI, 4.2-5.6] months; October 10, 2018). After the second planned interim analysis of 270 deaths, median OS was 21.6 months with margetuximab vs 19.8 months with trastuzumab (HR, 0.89; 95% CI, 0.69-1.13; P = .33; September 10, 2019), and investigator-assessed PFS showed 29% relative risk reduction favoring margetuximab (HR, 0.71; 95% CI, 0.58-0.86; P < .001; median, 5.7 vs 4.4 months; September 10, 2019). Margetuximab improved objective response rate over trastuzumab: 22% vs 16% (P = .06; October 10, 2018), and 25% vs 14% (P < .001; September 10, 2019). Incidence of infusion-related reactions, mostly in cycle 1, was higher with margetuximab (35 [13.3%] vs 9 [3.4%]); otherwise, safety was comparable. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, margetuximab plus chemotherapy had acceptable safety and a statistically significant improvement in PFS compared with trastuzumab plus chemotherapy in ERBB2-positive ABC after progression on 2 or more prior anti-ERBB2 therapies. Final OS analysis is expected in 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02492711.

Molecular characterization of gastric-type endocervical adenocarcinoma using next-generation sequencing.

Gastric-type endocervical adenocarcinoma is an uncommon aggressive type of endocervical adenocarcinoma that is not associated with human papillomavirus (HPV). At present, this tumor is classified under the spectrum of mucinous carcinoma of the uterine cervix. The clinical stage of gastric-type endocervical adenocarcinoma at the time of diagnosis is usually more advanced compared to the HPV-associated endocervical adenocarcinoma. Widespread dissemination to unusual sites, such as omentum, peritoneum, and distant organs, can be present. Owing to its rare incidence, diagnostic dilemmas, and aggressive behavior, clinical management can be challenging. In this study, we aimed to elucidate the molecular characteristics of these tumors by using next-generation sequencing (NGS) to assess 161 unique cancer-driver genes for single-nucleotide and copy-number variations, gene fusions, and insertions/deletions within gastric-type endocervical adenocarcinoma tumors. In total, 92 variants were detected across the 14 samples tested (7 variants on average per tumor). TP53 was the most recurrently mutated gene followed by MSH6, CDKN2A/B, POLE, SLX4, ARID1A, STK11, BRCA2, and MSH2. Abnormal p53 expression was observed in nine cases by immunohistochemistry, of which TP53 variants were present in four cases. MDM2 gene amplification in 12q15 (69202190-69233452) locus was seen in two cases that express normal p53 levels by immunohistochemistry. Four cases had STK11 null (frameshift/nonsense) variants, three of which were previously reported in Peutz-Jeghers syndrome. Overall, genes that are implicated in DNA damage, repair, cell cycle, Fanconi anemia pathway, and the PI3K-AKT signaling pathways were found to be mutated. Of note, genes known to have acquired and/or inherited variants in endometrial tumors were enriched within our cohort. In conclusion, our study shows the genetic heterogeneity of gastric-type endocervical adenocarcinoma with some potentially actionable molecular alterations, which highlights the importance of further molecular characterization for better identification of this rare entity, and hence better clinical management.

Evaluation of a comprehensive geriatric assessment tool in geriatric cancer patients undergoing adjuvant chemotherapy: a pilot study.

PURPOSE: It is recommended to use comprehensive geriatric assessment (CGA) in clinical oncology practice to improve care for geriatric cancer patients and to identify medical and social issues that may need further intervention. The purpose of this pragmatic pilot study was to evaluate the effectiveness of the Hurria et al. CGA in cancer patients 70 years of age or older undergoing adjuvant chemotherapy, as well as the feasibility of integrating it into a busy clinic practice and the psychosocial impact on these patients. METHOD: Twenty-five patients were recruited. Descriptive analysis was performed via a geriatric assessment questionnaire completed by the participants prior to their first adjuvant chemotherapy treatment and during follow-up, 2 to 6 weeks after last treatment. Additionally, study staff performed a geriatric healthcare assessment at both time points. RESULTS: The results of this pilot study show that administration is feasible despite some challenges. Administration of a CGA in a clinic setting presented some logistical issues with regard to time and space available in clinic. Analysis of patient data indicated only minor variations in patient domains from pre-chemo to post-chemo confirming previous research. Participants expressed gratitude for the extra time spent with them at a stressful time in their lives. CONCLUSION: Further information regarding the usefulness of a comprehensive geriatric assessment with regard to improving treatment selection, identifying undetected medical problems, and avoiding toxicity will be obtained if the administration of comprehensive geriatric questionnaires is incorporated into the clinic setting and considered into the allocated time for staff workload.

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

Enhancing accrual to chemotherapy trials for patients with early stage triple-negative breast cancer: a survey of physicians and patients.

PURPOSE: The optimal chemotherapy regimen for patients with early stage triple-negative breast cancer (TNBC) remains unknown. The purpose of the study is to survey physicians and breast cancer patients about preferred chemotherapy regimens for early stage TNBC and clinical trial strategies. METHODS: A standardised online questionnaire was developed and circulated to medical oncologists known to treat breast cancer. A separate questionnaire was given to patients who had received chemotherapy for breast cancer. RESULTS: The questionnaire was completed by 41/84 medical oncologists (48.8% response rate) and 74 patients. The most commonly used neoadjuvant and adjuvant chemotherapy regimens for TNBC were dose-dense doxorubicin and cyclophosphamide (AC)-paclitaxel (P), dose-dense AC followed by weekly P and fluorouracil, epirubicin, cyclophosphamide-docetaxel (FEC-D). The majority of medical oncologists (80%) would be willing to enrol patients in trials evaluating the most effective chemotherapy regimen for TNBC. Oncologists favoured a three arm trial design comparing currently available standard of care treatments (36%) and trials of novel or non-standard of care agents 22% (9/41). Sixty percent (41/74) of patients indicated that they would be willing to be enrolled in trials evaluating various adjuvant regimens for TNBC. Both oncologists and patients were interested in novel consent approaches such as using the integrated consent model. CONCLUSION: Optimisation of chemotherapy for TNBC is an important and unmet clinical need. It is apparent that various chemotherapy regimens are used for patients with early stage TNBC. The majority of medical oncologists and patients are interested in entering trials to optimise chemotherapy choices.

Biological insights into effective and antagonistic combinations of targeted agents with chemotherapy in solid tumors.

The potential for synergistic interactions between anticancer drugs has been used to justify combinations of agents in clinical trials. However, most combinations of targeted agents and chemotherapies have been tested in the clinic without previous systematic evaluation of their potential benefit. Preclinical studies may help in the identification of synergistic or antagonistic interactions. For antineoplastic therapies, these studies may reveal synergy or antagonism of the drug combinations. Synergy occurs when two agents given together produce higher antitumoral activity than the sum of each individual drug. This represents the ideal setting for the development of combinations of targeted agents and chemotherapies. On the other side, certain drug combinations have shown adverse results, indicative of an antagonistic effect. In this article, we review the preclinical molecular bases that justify approved combinations of targeted agents with chemotherapy including examples of synergistic and antagonistic combinations. We also discuss scenarios for rational associations of targeted agents based on biological data and propose strategies that may improve the success of combinations of anticancer agents.

Randomized feasibility study of de-escalated (every 12 wk) versus standard (every 3 to 4 wk) intravenous pamidronate in women with low-risk bone metastases from breast cancer.

OBJECTIVES: Despite substantial variability in individual risk of skeletal complications, patients with metastatic bone disease are treated with bisphosphonates at the same dose and dosing interval. This study assessed the feasibility of conducting a randomized trial of less frequent bisphosphonate administration in women with breast cancer and low-risk bone metastases. METHODS: A randomized feasibility study was conducted. Patients receiving intravenous bisphosphonates for ≥3 months and with low-risk baseline serum C-telopeptide (CTx) levels (<600 ng/L) were assigned to pamidronate 90 mg intravenously every 3 to 4 weeks (control) or every 12 weeks (de-escalated). CTx, bone alkaline phosphatase, and pain scores (Brief Pain Inventory and Functional Assessment of Cancer Therapy-Bone Pain) were collected every 12 weeks for 48 weeks. RESULTS: Fifty-four patients were approached, 44 consented, and 38 were randomized. Median age was 55 (range, 29 to 77) and median baseline CTx was 163 ng/L (range, 10 to 526). Fourteen control group participants (73.7%) and 13 de-escalated group participants (68.4%) maintained CTx in the low-risk range (P=0.64). All patients changing to higher-risk range had progressive extraskeletal disease. Compared with the control group, there was a time-dependent increase in CTx in the de-escalated group. There were no significant differences in bone alkaline phosphatase, Brief Pain Inventory, or Functional Assessment of Cancer Therapy-Bone Pain. CONCLUSIONS: It is feasible to conduct randomized trials of de-escalated pamidronate in low-risk women treated with ≥3 months of prior bisphosphonate therapy. De-escalated scheduling satisfied our predefined definition of noninferiority compared with 3- to 4-weekly treatment. Larger trials should assess whether increasing CTx levels with de-escalated therapy lead to higher rates of skeletal complications.

Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies.

BACKGROUND: Treatment decisions in recurrent breast cancer are usually based on the estrogen (ER), progesterone (PgR) and HER2 receptor status of the primary tumour. Retrospective studies suggest that discordance between receptor expression of primary and recurrent breast cancer exists. METHODS: A pooled analysis of individual patient data from two large prospective studies comprising biopsy of recurrent lesions obtained from consenting patients was undertaken. Tissue was analyzed for ER, PgR by immunohistochemistry and HER2 by FISH. Receptor status of recurrent disease was compared with that of the primary tumour. Recruiting clinicians assessed whether or not receptor discordance affected subsequent systemic treatment. RESULTS: Two hundred and eighty-nine patients underwent biopsy. Recurrent biopsy specimens were obtained from locoregional recurrence in 48.1% and from distant metastases in 51.9%. Distant sites included skin/soft tissue (25.0%), bone/bone marrow (19.2%) and liver (15.8%). Benign disease or second primary cancer was observed in 7.6% of biopsies. Discordance in ER, PgR or HER2 between confirmed primary and recurrent breast cancer was 12.6%, 31.2% and 5.5%, respectively (all p<0.001). Biopsy results altered management in 14.2% of patients undergoing biopsy (95% confidence intervals 10.4-18.8%, p≤0.0001). The duration between primary and recurrent disease, the site of recurrence and the receptor profile of the primary tumour did not affect discordance rates. CONCLUSIONS: There is substantial discordance in receptor status between primary and recurrent breast cancer. The number needed to biopsy in order to alter treatment was 7.1. Patients with recurrent breast cancer should have tissue confirmation of receptor status of recurrent disease.

Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer.

PURPOSE: Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. PATIENTS AND METHODS: Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. RESULTS: Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. CONCLUSION: Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

Filling in the gaps: reporting of concurrent supportive care therapies in breast cancer chemotherapy trials.

BACKGROUND: Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. METHODS: A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. RESULTS: Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). CONCLUSION: There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.

Defining ovarian failure in amenorrheic young breast cancer patients.

At present, there is no gold standard test for the investigation of ovarian function in pre-menopausal breast cancer patients who develop amenorrhea after chemotherapy. Clinical, biochemical and biophysical investigations continue to be utilized in clinical practice, despite concerns regarding their predictive value for menopause. The resulting uncertainty about a woman's actual menopausal status has important consequences for patient management. These include choice of appropriate endocrine therapy, assessment of residual ovarian function and its effect on breast cancer recurrence, fertility issues and the prediction of the likelihood of conception. It is hoped that the development of novel surrogates may allow clinicians to more accurately assess menopausal status and thereby facilitate tailored and individualised therapy for this common group of patients.

Assessing women at high risk of breast cancer: a review of risk assessment models.

Women who are at high risk of breast cancer can be offered more intensive surveillance or prophylactic measures, such as surgery or chemoprevention. Central to decisions regarding the level of prevention is accurate and individualized risk assessment. This review aims to distill the diverse literature and provide practicing clinicians with an overview of the available risk assessment methods. Risk assessments fall into two groups: the risk of carrying a mutation in a high-risk gene such as BRCA1 or BRCA2 and the risk of developing breast cancer with or without such a mutation. Knowledge of breast cancer risks, taken together with the risks and benefits of the intervention, is needed to choose an appropriate disease management strategy. A number of models have been developed for assessing these risks, but independent validation of such models has produced variable results. Some models are able to predict both mutation carriage risks and breast cancer risk; however, to date, all are limited by only moderate discriminatory accuracy. Further improvements in the knowledge of how to best integrate both new risk factors and newly discovered genetic variants into these models will allow clinicians to more accurately determine which women are most likely to develop breast cancer. These steady and incremental improvements in models will need to undergo revalidation.

Lapatinib and HER2 status: results of a meta-analysis of randomized phase III trials in metastatic breast cancer.

BACKGROUND: In vitro studies have shown that lapatinib is most active in HER2 over-expressing tumors, but also has activity in cell lines over-expressing HER1. Consequently, clinical testing of lapatinib has been carried out in both HER2-positive and HER2-negative patients. Here we evaluate the clinical efficacy of lapatinib in HER2-positive and HER2-negative patients. METHODS: A published data meta-analysis of randomized trials that evaluated the efficacy of combining lapatinib with chemo- or endocrine therapy in patients with metastatic breast cancer was undertaken. Hazard ratios (HR) were extracted for progression free survival (PFS) and overall survival, while odds ratios were extracted for disease stabilization, serious adverse events (SAEs) and need for discontinuation. Pooled estimates were computed using inverse-variance and random-effect modeling. RESULTS: Three randomized controlled trials with a total of 2264 patients met the inclusion criteria. Meta-analysis demonstrated the HR for PFS with lapatinib was 0.69 in patients with HER2-positive disease, while there was no improvement in PFS (HR=0.98, 95% CI 0.80-1.19) for treatment of HER2-negative breast cancer. Similarly, overall survival was improved in HER2-positive patients (HR 0.76, 95% CI 0.60-0.96), but not in HER2-negative patients (HR 0.89, 95% CI 0.65-1.21). Patients on lapatinib were 64% more likely to develop a SAE and 2.3 times more likely to discontinue therapy due to toxicity. CONCLUSION: Clinical benefit from treatment with lapatinib is limited to patients with HER2-positive breast cancer. Outside of the clinical trial setting, lapatinib should not be administered to women with HER2-negative disease because it causes increased toxicity without improving disease outcome.

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases.

BACKGROUND: Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D(3). This study therefore aimed to assess the effect of this dose of vitamin D(3) in patients with bone metastases from breast cancer. METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D(3) and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. RESULTS: Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity. CONCLUSIONS: Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption.

Predicting benefit from fulvestrant in pretreated metastatic breast cancer patients.

Fulvestrant use in pretreated metastatic breast cancer patients is associated with variable response rates. This study aimed to characterize these responses and to develop a prediction model to identify those patients who could potentially derive the most clinical benefit. A nationwide review of patients enrolled in a Canadian compassionate use program from 1999 to 2006 was performed. Prior therapy with tamoxifen, steroidal, and nonsteroidal aromatase inhibitors was mandatory. The dependent variable in the analysis was the proportion of patients requiring chemotherapy at 3 months following the start of fulvestrant. General Linear Mixed modeling was used to identify factors significantly associated with this dependant variable and to subsequently develop the prediction model. Three hundred and five women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Median duration of fulvestrant treatment was 4.1 months (range 0.8-63.1). Factors predictive of being chemotherapy free at 3 months included older age, no prior adjuvant hormonal therapy, and the absence of lung or brain metastases at the start of therapy. A receiver operating characteristic (ROC) curve analysis had an area under the curve of 0.70 (95% CI 0.60-0.80). This model was able to identify risk information that could be helpful in assessing which patients would most likely benefit from fulvestrant as an intervention with the objective being a delay in chemotherapy.

The role of palliative care in the lung cancer patient: can we improve quality while limiting futile care?

PURPOSE OF REVIEW: Lung cancer is the leading cause of cancer death worldwide, and is diagnosed in the advanced stage in 70% of patients. This study will summarize the most up-to-date strategies in supportive care for patients with metastatic lung cancer. RECENT FINDINGS: Two recent systematic reviews concluded that longer-course radiation treatment offers a survival and symptom benefit over short-course treatment in patients with good performance status. Whereas several meta-analyses have demonstrated the benefit of palliative chemotherapy for quality of life and survival, the optimal drug combination and number of courses remain under study, and proper stratification of patients is essential. Clinical practice guidelines are available for evidence-based management of symptoms common in patients with lung cancer. Early integration of specialized palliative care shows promise as a means of improving patient care and limiting unnecessary treatment. SUMMARY: Supportive care for the patient with advanced lung cancer should involve consideration and discussion of all therapeutic options that could provide benefit. Depending on the clinical situation, these could include chemotherapy or radiation, and should always include appropriate symptom management and family support. Research incorporating symptom and quality-of-life measures is challenging, but is also essential to inform excellent supportive care.