Robin Zon

Breast Cancer Adjuvant Chemotherapy Decisions in Older Women: The Role of Patient Preference and Interactions With Physicians

PURPOSE Breast cancer chemotherapy decisions in patients > or = 65 years old (older) are complex because of comorbidity, toxicity, and limited data on patient preference. We examined relationships between preferences and chemotherapy use. METHODS Older women (n = 934) diagnosed with invasive (> or = 1 cm), nonmetastatic breast cancer from 2004 to 2008 were recruited from 53 cooperative group sites. Data were collected from patient interviews (87% complete), physician survey (93% complete), and charts. Logistic regression and multiple imputation methods were used to assess associations between chemotherapy and independent variables. Chemotherapy use was also evaluated according to the following two groups: indicated (estrogen receptor [ER] negative and/or node positive) and possibly indicated (ER positive and node negative). RESULTS Mean patient age was 73 years (range, 65 to 100 years). Unadjusted chemotherapy rates were 69% in the indicated group and 16% in the possibly indicated group. Women who would choose chemotherapy for an increase in survival of < or = 12 months had 3.9 times (95% CI, 2.4 to 6.3 times; P < .001) higher odds of receiving chemotherapy than women with lower preferences, controlling for covariates. Stronger preferences were seen when chemotherapy could be indicated (odds ratio [OR] = 7.7; 95% CI, 3.8 to 16; P < .001) than when treatment might be possibly indicated (OR = 1.9; 95% CI, 1.0 to 3.8; P = .06). Higher patient rating of provider communication was also related to chemotherapy use in the possibly indicated group (OR = 1.9 per 5-point increase in communication score; 95% CI, 1.4 to 2.8; P < .001) but not in the indicated group (P = .15). CONCLUSION Older womens preferences and communication with providers are important correlates of chemotherapy use, especially when benefits are more equivocal.

Management strategies and outcomes of germ cell tumor patients with very high human chorionic gonadotropin levels.

PURPOSE To determine the therapeutic results in advanced germ cell tumor (GCT) patients with initial human chorionic gonadotropin (hCG) elevation greater than 50,000 mIU/mL and to document the levels of hCG decline and subsequent plateau and outcome of this patient population. PATIENTS AND METHODS We conducted a retrospective review of 41 patients who presented to Indiana University (IU) with hCG levels greater than 50,000 mIU/mL between December 1976 and August 1996. All patients had received cisplatin-containing regimens and were monitored with serial hCG levels. RESULTS Twenty-two of 41 (53.7%) patients continuously show no evidence of disease (NED) and eight additional patients (19.5%) are currently NED with salvage therapy. Only two of 41 patients had a normal hCG level at the start of the fourth and final course of cisplatin combination chemotherapy. Eight additional patients showed normalized hCG levels 1 month later. Seven of these 10 are continuously NED and three are currently NED with salvage therapy. Thirty-one patients had an abnormal hCG greater than 1 month after they completed primary chemotherapy; 15 of these patients (48%) are continuously NED despite no further therapy and five additional patients (16%) are currently NED with salvage therapy. Overall, there was an initial rapid decline in hCG followed by a plateau after the first two courses of therapy. CONCLUSION Less than 10% of patients who present with hCG levels greater than 50,000 mIU/mL will have a normal hCG at the institution of the fourth and final course of chemotherapy. However, 22 of 41 (53.7%) are continuously NED despite no further therapy. We feel that the optimal strategy for such patients is monthly observation with initiation of salvage therapy if and when there is serologic progression.

American Society of Clinical Oncology Statement: Biosimilars in Oncology

As many biosimilars come to market in the next several years, their use in oncology will play an important role in the future care of patients with cancer. ASCO is committed to providing education and guidance to the oncology community on the use of biosimilars in the cancer setting; therefore, ASCO has developed this statement to offer guidance in the following areas: (1) naming, labeling, and other regulatory considerations, (2) safety and efficacy of biosimilars, (3) interchangeability, switching, and substitution, (4) value of biosimilars, and (5) prescriber and patient education.

Association of 70-Gene Signature Assay Findings With Physicians’ Treatment Guidance for Patients With Early Breast Cancer Classified as Intermediate Risk by the 21-Gene Assay

Importance Among patients who undergo the 21-gene assay (21-GA), 39% to 67% receive an intermediate risk result and may receive ambiguous treatment guidance. The 70-gene signature assay (70-GS) may be associated with physicians’ treatment decisions in this population with early breast cancer. Objective To determine whether 70-GS findings are associated with physicians’ decisions about adjuvant treatment and confidence in their recommendations and to evaluate the dichotomous (high- vs low-risk) and continuous distribution of 70-GS indices among this group of patients with intermediate risk. Design, Setting, and Participants The Prospective Study of MammaPrint in Breast Cancer Patients With an Intermediate Recurrence Score (PROMIS trial) was an impact study conducted from May 20, 2012, through December 31, 2015, that enrolled 840 patients with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30. Patients were treated in 58 US institutions. Interventions The 70-GS result was given to physicians before adjuvant treatment. Main Outcomes and Measures Change in physician treatment decision before vs after receiving the 70-GS result. With a treatment change of greater than 20%, the odds ratio (OR) was applied. Results Among the 840 patients who underwent 70-GS classification (mean age, 59 years; range, 27-93 years), 374 (44.5%) had a low-risk and 466 (55.5%) had a high-risk result. The distribution of 70-GS indices did not correlate with recurrence score within the 21-GA intermediate range, with 70-GS low- and high-risk patients observed at every recurrence score. A significant change in adjuvant treatment was associated with receiving the 70-GS classifications with an OR of 0.64 (95% CI, 0.50-0.82; McNemar test, P < .001) for all patients. Among the low-risk patients, 108 of 374 (28.9%) had chemotherapy removed from their treatment recommendation; among the high-risk patients, 171 of 466 (36.7%) had chemotherapy added. Results of the 70-GS were associated with the physician’s adjuvant treatment recommendation; 409 high-risk patients (87.8%) were recommended to receive adjuvant chemotherapy, and 339 low-risk patients (90.6%) were recommended no chemotherapy. Physicians reported having greater confidence in their treatment recommendation in 660 cases (78.6%) based on 70-GS results. Conclusions and Relevance The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results.

Phase I Study of Amrubicin and Cyclophosphamide in Patients With Advanced Solid Organ Malignancies: HOG LUN 07-130

Objectives: Relapsed small cell lung cancer (SCLC) has limited treatment options. Anthracyclines and cyclophosphamide have shown synergy in many tumors. Amrubicin (AMR) and cyclophosphamide both have single-agent activity in SCLC. This phase I trial evaluated the combination of AMR and cyclophosphamide in refractory solid organ malignancies and in relapsed SCLC. Materials and Methods: The primary endpoint was to determine maximum-tolerated dose and dose-limiting toxicities of the combination. Eligible patients were enrolled in sequential dose escalation cohorts in a standard 3+3 design. Treatment consisted of cyclophosphamide IV at 500 mg/m2 on day 1 with escalating doses of AMR IV on days 1 to 3 (25 to 40 mg/m2 with increments of 5 mg/m2 per cohort). Cycles were repeated every 21 days. Exploratory objectives analyzed the presence of NQO1 polymorphisms and topoisomerase IIA amplification and correlation with response. Results: Thirty-six patients were enrolled, of whom 18 patients had SCLC (50%). Maximum-tolerated dose was determined to be dose level 2 (cyclophosphamide 500 mg/m2, AMR 30 mg/m2) due to grade 4 thrombocytopenia. The main grade 3 to 4 toxicities were hematologic. Efficacy results are available for 34 patients. Partial responses, stable disease, and progressive disease rates in the overall study population were 20.6% (n=7), 38.2% (n=13), and 41.2% (n=14), respectively. Partial response, stable disease, and progressive disease rates in the SCLC patients and 1 patient with extrathoracic small cell were 36.8% (n=7), 26.3% (n=5), and 36.8% (n=7), respectively. There was no correlation between topoisomerase IIA amplification or NQO1 polymorphisms and response. Conclusions: AMR and cyclophosphamide can be safely combined with little activity observed in heavily pretreated SCLC patients.

ReCAP: Clinical Trial Assessment of Infrastructure Matrix Tool to Improve the Quality of Research Conduct in the Community

PURPOSE Several publications have described minimum standards and exemplary attributes for clinical trial sites to improve research quality. The National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) developed the clinical trial Best Practice Matrix tool to facilitate research program improvements through annual self-assessments and benchmarking. The tool identified nine attributes, each with three progressive levels, to score clinical trial infrastructural elements from less to more exemplary. The NCCCP sites correlated tool use with research program improvements, and the NCI pursued a formative evaluation to refine the interpretability and measurability of the tool. METHODS From 2011 to 2013, 21 NCCCP sites self-assessed their programs with the tool annually. During 2013 to 2014, NCI collaborators conducted a five-step formative evaluation of the matrix tool. RESULTS Sites reported significant increases in level-three scores across the original nine attributes combined (P<.001). Two specific attributes exhibited significant change: clinical trial portfolio diversity and management (P=.0228) and clinical trial communication (P=.0281). The formative evaluation led to revisions, including renaming the Best Practice Matrix as the Clinical Trial Assessment of Infrastructure Matrix (CT AIM), expanding infrastructural attributes from nine to 11, clarifying metrics, and developing a new scoring tool. CONCLUSION Broad community input, cognitive interviews, and pilot testing improved the usability and functionality of the tool. Research programs are encouraged to use the CT AIM to assess and improve site infrastructure. Experience within the NCCCP suggests that the CT AIM is useful for improving quality, benchmarking research performance, reporting progress, and communicating program needs with institutional leaders. The tool model may also be useful in disciplines beyond oncology.

Qualitative analysis of practicing oncologists’ attitudes and experiences regarding HIT-facilitated collection of patient-reported outcomes.

56 Background: Growing interest in incorporating widespread and routine collection of patient-reported outcomes (PROs) into a rapid-learning system for cancer care motivates consideration of stakeholder attitudes and experiences with PRO collection. Practicing oncologists are stakeholders whose views are not well characterized to date. METHODS We developed an interview guide after literature review and 6 in-depth interviews with leaders in the field. With IRB approval, we conducted 45-minute semi-structured interviews with medical oncologists identified through affiliation with QOPI or a minority-based CCOP. Purposive sampling ensured a diverse range of viewpoints. Interviews were conducted until thematic saturation. Multiple analysts independently reviewed and thematically coded verbatim transcripts. RESULTS 17 interviews were conducted with oncologists from diverse practice settings and types. Emergent themes included variability in understanding and experience with PRO collection; general enthusiasm for the potential value of PROs (with subthemes focused on impact on thoroughness and efficiency, and potential for coordination with quality measurement processes); and fundamental concerns (including information overload, the possibility of identifying problems for which no good interventions exist, depersonalization of the physician-patient encounter, cost, and inefficiency). Several potential barriers to the widespread implementation of PROs were identified, including need for buy-in from other stakeholders in the practice, lack of appropriate referral resources, staffing needs, and technology concerns. Respondents generally favored simple tools, format allowing for time-trending and visualization of the impact of interventions, and tailoring to the individual patients disease site, stage, and point in treatment trajectory. Very few identified patient compliance, data sharing/privacy, or medical liability as major barriers to implementation. CONCLUSIONS Widespread inclusion of PROs in a rapid-learning system of oncology care will require careful consideration of the insights provided by practicing oncologists.