Lubna Chaudhary

Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

Objective. The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT3) antagonists in revolutionizing the management of platinum-based chemotherapy–induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT3 antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting clearly endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. Methods. Data for patients (n¼159) receiving platinum-based chemotherapy regimens were retrospectively collected. Patients getting 5-HT3 antagonists without steroids or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and Eastern Cooperative Oncology Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of >grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic efficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. Results. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron (n¼157), granisetron (n¼81), and ondansetron (n¼131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p¼0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p¼0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting (p¼0.15 and p¼0.63, respectively). However, complete nausea control was significantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p50.05). Conclusion. No significant difference exists in the antiemetic efficacy of the three 5-HT3 antagonists studied in controlling CINV when administered in combination with dexamethasone. Choice of antiemetic regimen should therefore be based on drug cost.

Peripheral blood stem cell mobilization in multiple myeloma patients treat in the novel therapy-era with plerixafor and G-CSF has superior efficacy but significantly higher costs compared to mobilization with low-dose cyclophosphamide and G-CSF

Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low‐dose cyclophosphamide (LD‐CY) and granulocyte‐colony stimulating factor (G‐CSF) against plerixafor and G‐CSF, in multiple myeloma (MM) patients treated in the novel therapy‐era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1‐year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD‐CY (1.5 gm/m2) and G‐CSF (n = 74) were compared against patients receiving plerixafor and G‐CSF (n = 33). Compared to plerixafor, LD‐CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 106/kg vs. 2.4 × 106/kg, P = 0.001). Six patients (8.1%) in the LD‐CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 106/kg vs. 7 × 106/kg; P‐value = 0.001). Mobilization with LD‐CY was associated with increased (albeit statistically non‐significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD‐CY group (

Perception of cancer recurrence risk: more information is better.

28,980 vs.

Weight change associated with third-generation adjuvant chemotherapy in breast cancer patients.

19,626.5 P‐value < 0.0001). In conclusion, in MM plerixafor‐based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD‐CY mobilization. Our data caution against the use of LD‐CY in MM patients for mobilization, especially after induction with lenalidomide‐containing regimens. J. Clin. Apheresis 28:359–367, 2013.

Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score.

OBJECTIVE Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk. METHODS A survey was conducted on women with a prior breast cancer (n=141). RESULTS Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence. CONCLUSIONS Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk. PRACTICE IMPLICATIONS Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer.

Is hematopoietic cell transplantation still a valid option for mantle cell lymphoma in first remission in the chemoimmunotherapy-era?

BACKGROUND Studies have shown that breast cancer treatment can cause an increase in weight. Weight gain during chemotherapy is usually significant and may be associated with poor survival. However, the role of third- generation chemotherapy regimens and weight gain is not well reviewed. METHODS We retrospectively analyzed the mean percentage weight change during the first year after breast cancer diagnosis in 246 patients at West Virginia University during September 2007 and October 2010. Kruskal-Wallis test and post hoc pairwise comparisons were used to assess the influence of age, histology, stage, ER/PR/HER2/neu status, menopausal status, and types of therapeutic modalities received on the percentage weight change. Kaplan-Meier method with log-rank test was used to evaluate recurrence-free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free patients were censored at last follow-up. RESULTS Mean weight gain was 0.39% (SD, 0.40) of baseline body weight, 1 year after diagnosis of breast cancer. Premenopausal status was the only factor associated with significant weight gain (+1.67% vs -0.10% for postmenopausal patients; P = .02). Stages ≥ III was associated with significant weight loss (-1.64% for stages III, IV vs +0.85% for stages 0, I, II; P = .02) and a lower RFS at 3 years and 5 years (P < .0001). Higher baseline weight (> 90th percentile) did not have any significant impact on RFS (0.84 vs 0.91; P = .19). There was no significant change in weight relative to other factors. CONCLUSIONS Our study in patients receiving third-generation adjuvant chemotherapy regimens did not show any significant change in percentage weight with chemotherapy. Premenopausal status was the only significant factor associated with weight gain. As expected, stage III or higher disease was associated with significant weight loss and lower RFS.

Triple-Negative Breast Cancer: Who Should Receive Neoadjuvant Chemotherapy?

OBJECTIVE/BACKGROUND Progesterone-receptor negativity (PR-) is predictive of adverse outcomes in estrogen receptor-positive (ER+) breast cancer. The Oncotype DX assay provides risk stratification for hormone receptor-positive (HR+) invasive breast cancer; however, the association of PR status and Oncotype DX recurrence scores (RSs) is less clear. METHODS We designed an analysis to determine whether a significant difference exists in the RS for ER+/PR- tumors when compared with ER+/PR+ breast cancer. Three hundred and fifty patients with HR+ invasive breast cancer who underwent Oncotype DX testing at our institution from December 2006 to October 2013 were included. We also examined the concordance in the HR status reported by immunohistochemical (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. The data were analyzed by analysis of variance, F test, t test, and chi-square tests. Multivariate linear regression was used to determine significant predictors of Oncotype DX RS. RESULTS A total of 301 patients had ER+/PR+ tumors and 47 patients had ER+/PR- tumors by IHC. PR- tumors had a significantly higher RS than PR+ tumors (24.7±8.53 vs. 17.3±7.38; p<.001), predicting a greater 10-year risk of distant recurrence. Multivariate linear regression showed PR status and tumor grade to be significant predictors of Oncotype DX RS (p<.0001). A total of 284 patients had HR status reported by Oncotype DX assay. Concordance between IHC and RT-PCR was 99.3% for ER and 88.7% for PR. CONCLUSION Our study shows that ER+/PR- breast cancer tumors are associated with a significantly higher Oncotype DX scores; this interprets into a higher risk of recurrence. Our data also show that the concordance between IHC and RT-PCR was 99.3% for ER and lower at 88.7% for PR.

Abstract P6-09-37: Ductal carcinoma in situ: Patient outcomes and association with hormone receptors

Modern chemoimmunotherapies have produced higher response rates and improved survival in mantle cell lymphoma (MCL); however, disease relapse remains a challenge. The availability of various post-remission maintenance or consolidation strategies, have led some to question the role of upfront autologous hematopoietic cell transplantation (auto-HCT) consolidation for MCL, in the chemoimmunotherapy-era. A one size fits all approach is no longer appropriate for MCL in first remission, and the choice of preferred post-remission (observation, maintenance or consolidation) strategy is increasingly becoming a factor of patient age, comorbidities and disease risk stratification. In select low-risk patients (based on Mantle cell lymphoma International Prognostic Index (MIPI)), observation following rituximab plus Hyper-CVAD-like inductions seems appropriate. Rituximab maintenance after anthracycline-based chemoimmunotherapies in elderly transplant ineligible patients has shown survival benefit and should be considered a valid option. Limited studies suggest feasibility of radioimmunotherapy consolidation in first remission; however, in the absence of randomized data, this modality remains investigational. In younger, transplant-eligible patients receiving cytarabine-containing inductions, upfront consolidation with auto-HCT has shown survival benefit, and remains a standard-of-care option in the modern-era. Hyper-CVAD associated stem cell mobilization failure is an increasingly recognized problem, underscoring the need for alternative inductions, or consideration for early stem cell collection, when this induction regimen is used. Outcomes of high-risk MIPI patients remain suboptimal with currently available induction and post-remission strategies and represents an area where adoptive immunotherapy in the form of allogeneic-HCT warrants investigation. Incorporation of novel MoAbs and targeted agents (PI3K inhibitors, mTOR inhibitors, BTK inhibitors and so on.) in maintenance and consolidation strategies will build on the significant therapeutic gains of last decade, in coming years.

Abstract P4-11-31: Inverse relationship between ER+/PR- breast cancer and OncotypeDx scores and concordance between IHC and RT-PCR

Progress in the treatment of triple-negative breast cancer remains an important challenge. Given the aggressive biology and high risk of distant recurrence, systemic chemotherapy is warranted in most patients. Neaodjuvant chemotherapy benefits patients with locally advanced disease by downsizing the tumor and increasing the probability of breast-conserving surgery. Clinical and pathologic responses provide important prognostic information, which makes neoadjuvant therapy an attractive approach for all patients with triple-negative breast cancer. Clinical research in the neoadjuvant setting is focused on improvement in pathologic complete response rates and outcomes of patients with residual disease.

Weight change in patients with treatment of breast cancer.

Background Local recurrence is a major concern in patients (pts) diagnosed with ductal carcinoma in situ (DCIS). Therefore, the need to identify pts at risk for DCIS recurrence is a significant priority. In invasive breast cancers, ER+/PR- subtype is considered a more aggressive tumor phenotype with poorer prognosis as compared to ER+/PR+ tumors. It is unclear whether this molecular subtype holds the same significance in pts with DCIS. Methods We designed an analysis to determine if a significant difference exists in the recurrence rates in pts with ER+/PR- DCIS when compared to ER+/PR+ tumors. Six hundred and ninety three pts diagnosed and treated for DCIS at Froedtert & MCW Clinical Cancer Center from Feb 2002-March 2015 were included in our study. Recurrence was defined as either non-invasive or invasive ipsilateral, contralateral or distant disease. Probabilities of recurrences were calculated using Kaplan-Meier estimator. Cox proportional hazards model was used to evaluate the effect of prognostic factors on DCIS recurrence. Results Median follow up was 5.2 years. Five year recurrence free survival (RFS) was 91% (95% CI 88.2-93.3) while estimated 7 year RFS was 86% (95% CI 81.9-89.2). Patient characteristics are shown in table below. Seventy five pts were found to have a recurrence during their follow-up. Most of the grade 1 tumors were ER+/PR+ whereas almost all of the ER-/PR- subtype were high grade tumors. ER+/PR- tumors were mainly intermediate and high grade (p Conclusion ER+/PR- subtype was not a significant predictor of recurrence in DCIS patients. This finding is in contrast to the risk of recurrence and tumor aggressiveness seen in invasive breast cancers. Mastectomy and post lumpectomy radiation were associated with improved outcomes as was adjuvant endocrine therapy. Citation Format: Chaudhary LN, Jawa Z, Hanif A, Szabo A, Chitambar CR. Ductal carcinoma in situ: Patient outcomes and association with hormone receptors [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-37.