Faculty Bibliography

OBJECTIVES: To evaluate the efficacy and safety of irinotecan and bevacizumab in recurrent ovarian cancer. The primary objective was to estimate the progression free survival (PFS) rate at 6months. Secondary objectives included estimation of overall survival (OS), objective response rate (ORR), duration of response, and an evaluation of toxicity. METHODS: Recurrent ovarian cancer patients with no limit on prior treatments were eligible. Irinotecan 250mg/m2 (amended to 175mg/m2 after toxicity assessment in first 6 patients) and bevacizumab 15mg/kg were administered every 3weeks until progression or toxicity. Response was assessed by RECIST or CA-125 criteria every 2cycles. RESULTS: Twenty nine patients enrolled (10 were platinum-sensitive and 19 were platinum-resistant). The median number of prior regimens was 5 (range 1-12); 13 patients had prior bevacizumab and 11 prior topotecan. The PFS rate at 6months was 55.2% (95% CI: 40%-77%). The median number of study cycles given was 7 (range 1-34). Median PFS was 6.8months (95% CI: 5.1-12.1months); median OS was 15.4months (95% CI: 11.9-20.4months). In this study, no complete response (CR) was observed. The objective response rate (ORR; PR or CR) for all patients entered was 27.6% (95% CI: 12.7%-47.2%) and the clinical benefit rate (CR+PR+SD) was 72.4% (95% CI: 52.8%-87.3%); twelve patients experienced duration of response longer than 6months. In the 24 patients with measurable disease, a partial response (PR) was documented in 8 (30%) patients; 13 patients maintained stable disease (SD) at first assessment. The most common grade 3/4 toxicity was diarrhea. No treatment-related deaths were observed. CONCLUSIONS: Irinotecan and bevacizumab has activity in heavily pre-treated patients with recurrent ovarian cancer, including those with prior bevacizumab and topoisomerase inhibitor use.

BACKGROUND: Certain vulnerability factors have been found to place patients at risk for depression and anxiety, especially within the context of medical illness. OBJECTIVES: We sought to describe the relationships among early childhood adversity (ECA) and anxiety, depression and distress in patients with breast cancer. METHODS: Patients with breast cancer (stages 0-IV) were assessed for ECA (i.e., the Risky Families Questionnaire subscales include Abuse/Neglect/Chaotic Home Environment), distress (i.e., Distress Thermometer and Problem List), anxiety (Hospital Anxiety and Depression Scale-Anxiety), depression (Hospital Anxiety and Depression Scale-Depression), meeting standardized cut-off thresholds for distress (Distress Thermometer and Problem List >/=4 or >/=7)/anxiety (Hospital Anxiety and Depression Scale-Anxiety >/=8)/depression (Hospital Anxiety and Depression Scale-Depression >/=8) and demographic factors. RESULTS: A total of 125 participants completed the study (78% response rate). ECA was associated with depression (p <0.001), anxiety (p = 0.001), and distress (p = 0.006), meeting cut-off threshold criteria for distress (p = 0.024), anxiety (p = 0.048), and depression (p = 0.001). On multivariate analysis, only depression (p = 0.04) and emotional issues (i.e., component of Distress Thermometer and Problem List) (p = 0.001) were associated with ECA. Neglect, but not Abuse and Chaotic Home Environment, was associated with depression (beta = 0.442, p < 0.001), anxiety (beta = 0.342, p = 0.002), and self-identified problems with family (beta = 0.288, p = 0.022), emotion (beta = 0.345, p = 0.004), and physical issues (beta = 0.408, p < 0.001). CONCLUSION: ECA and neglect are associated with multiple psychologic symptoms, but most specifically depression in the setting of breast cancer. ECA contributes to psychologic burden as a vulnerability factor. ECA may help to explain individual patient trajectories and influence the provision of patient-centered care for psychologic symptoms in patients with breast cancer.

Historically, neoadjuvant chemotherapy (NACT) was extrapolated from adjuvant regimens. Dual HER2 blockade and the introduction of carboplatin for triple negative breast cancers (TNBC) emerged by December 2013 and have improved pathological complete response (pCR) rates. The objective of this study was to assess the pCR rates before and after the introduction of these new neoadjuvant regimens. Materials and Methods. Stage I-III breast cancer patients who received NACT were analyzed for rates of pCR by clinical characteristics (i.e., age, BMI, axillary lymphadenopathy, and histologic subtype), by time period (1 = 3/2010-11/2013, 2 = 12/2013-3/2015), and by type of chemotherapy (e.g., anthracycline/taxane only, carboplatin-containing, and HER2 blockade). Results. 113 patients received NACT. Overall pCR rate was 26.5 percent (n = 30). The pCR rate increased from 14% to 43.1% (p = 0.001) from time period 1 to time period 2 and were associated with HER2 positivity (p = 0.003), receiving treatment during time period 2 (p = 0.001) and using an anthracycline/taxane plus additional agent type of regimen (p = 0.004). Conclusions. Our study revealed a significant difference in rates of pCR over five years. Window of opportunity trials and other trials that utilize pCR analysis should be encouraged.

We are reporting a case of a 34-year-old woman with occult primary breast cancer discovered after initially presenting with neurological symptoms. She was successfully treated with neoadjuvant chemotherapy followed by definitive axillary lymph node dissection and ipsilateral whole breast radiotherapy. The case presented is unique due to the rarity of occult primary breast cancer, especially in light of her initial confounding neurological signs and symptoms, which highlights the importance of careful staging.

INTRODUCTION: Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). METHODS: The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting >/=6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. RESULTS: We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with >/= grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. CONCLUSION: Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in combination with everolimus with continuing responses. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01127763.

BACKGROUND: Continuous-infusion topotecan with erlotinib has the potential to reverse topotecan resistance due to drug efflux mechanisms. We assessed the activity of such a regimen in ovarian cancer patients previously failing bolus topotecan. Assay for shed collagen epitopes recognized by antibody HU177 during treatment explored its ability to reflect tumor invasion. METHODS: Topotecan 0.4 mg/m(2) per day was administered by continuous infusion for 9-10 days every 3 weeks. Erlotinib, 150 mg orally, was administered on days 1-10 of each cycle. Cycles were repeated until progression or toxicity. Serum for shed HU177 collagen epitopes was collected weekly. This was a two-stage design to detect a CA-125 response rate of at least 20% in 30 patients after completing two treatment cycles. The trial would be terminated early if there were less than two CA-125 responses in 16 patients. Four or more CA-125 responses in 30 patients would justify further study of this regimen in prior topotecan treatment failures. RESULTS: Six patients were enrolled, with four receiving three or more cycles and one achieving a partial response by cancer antigen 125 (CA-125) criteria. Shed epitope levels became undetectable on at least one measurement in all patients who received three or more cycles (Fig. 1A) and reappeared concomitantly with rises in CA-125 and clinical progression (Fig. 1B). After logistical delays, the trial was closed by the sponsor's decision to stop developing erlotinib in ovarian cancer. FIGURE 1: Monitoring of combination treatment. A, B, C, D, and F refer to patients. (A):: Topotecan and erlotinib. (B):: CA-125 in units/mL. CONCLUSION: Continuous-infusion topotecan with erlotinib was found safe in six pretreated ovarian cancer patients; one met CA-125 criteria for partial response. Serial shed epitope levels to reflect invasiveness deserve further study.