doxorubicin and carboplatin

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Median age of the cohort was 53 years. By continuing to use our website, you are agreeing to, Cancer Epidemiology, Biomarkers & Prevention, Collection: Targeting the Tumor Microenvironment, https://doi.org/10.1158/1538-7445.SABCS18-P1-15-14, Cancer Epidemiology, Biomarkers, & Prevention. In the standard arm, bevacizumab was given as 15 mg/kg on day 1, followed by gemcitabine (1,000mg/m on days 1 and 8) and carboplatin (AUC4 on day 1) every 3 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Evidence also suggests that pegylated liposomal doxorubicin-based treatment is more effective in patients with BRCA-mutated ovarian cancer. We hypothesized that the doublet of DOX+CAR is effective and tolerable in the neoadjuvant setting for TNBC and that tumor genomics may aid in determining those patients most likely to benefit. A total of 682 patients with recurrent ovarian cancer suitable for platinum-based retreatment were randomized 1:1 to standard treatment (CG-BEV) or the experimental treatment (CD-BEV). Grade 3 thrombocytopenia (2 pts), pruritis (1 pt), and mucositis (1 pt) were observed. Structural variants, such as amplifications, rearrangements, and frameshifts were the most frequent alterations detected. Tumor genomic profiling was done to determine the mutational spectrum, association of this spectrum in primary tumors with achieving pCR, and identifying alternative treatment strategies for PDX evaluation for patients with resistant disease. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Rutgers School of Public Health-Biostatistics, Piscataway, NJ; Rutgers New Jersey Medical School- Pathology, Newark, NJ; Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. In the experimental arm, bevacizumab was given at 10 mg/kg on day 1 and 15 followed, by pegylated liposomal doxorubicin (30 mg/m on day 1) and carboplatin (AUC5 on day 1) every 4 weeks for up to 6 cycles in the absence of progression disease or unacceptable toxicities. Patients received 4 cycles of neoadjuvant carboplatin (AUC 5) and liposomal doxorubicin (30mg/m2) administered every 28 days, then underwent definitive breast surgery followed by 12 weeks of adjuvant paclitaxel 80 mg/m2 administered weekly. Primary and secondary clinical endpoints were rate of pCR and two year recurrence free survival (RFS) and overall survival (OS), respectively. Global quality-of-life scores favored CD-BEV, but the difference was not significant over time. ovarian cancer doxil topotecan gynecologic oncology debates figure recurrent As an add-on to bevacizumab (Avastin), carboplatin plus pegylated liposomal doxorubicin (CD-BEV) significantly extended progression-free survival (PFS) compared with carboplatin and gemcitabine (CG-BEV) in patients with recurrent ovarian cancer whose first disease recurrence was >6 months after first-line platinum-based chemotherapy. It is known that platinum-sensitive recurrence is enriched for HRD-deficient patients and that carboplatin plus pegylated liposomal doxorubicin may be more effective in such patients. https://doi.org/10.1158/1538-7445.SABCS18-P1-15-14. Biologic PFS by serum CA 125 was a median of 11.5 months with CD-BEV compared with a median of 10.0 months with CG-BEV (HR, 0.758; 95% CI, 0.641-0.896; stratified log-rankP= .001). Our prior trial combining carboplatin (CAR) with liposomal doxorubicin (DOX) for metastatic TNBC showed good response rates with minimal side effects while allowing for greater platinum dosing compared to a taxane combination. Grade 5 AEs occurred in 11 patients (1.7%) between the 2 arms, 7 from standard therapy and 4 from the experimental treatment. Of the 25 pts who had residual disease, PDX was attempted from 14 pts, and 10 (71%) PDX were established, including those for all 3 patients experiencing recurrence. Abstract 933O. 2022 MJH Life Sciences and Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways. Fresh residual tumor samples were obtained at time of surgery for generation of patient derived xenografts (PDX). Citation Format: Chan N, Riedlinger GM, Lu S-e, Pham KT, Kirstein LJ, Eladoumikdachi FG, George MA, Potdevin LB, Kowzun MJ, Desai SA, Tang DM, Omene CO, Wong ST, Rodriguez-Rust L, Kumar S, Kearney TJ, Liu C, Ganesan S, Toppmeyer DL, Hirshfield KM. N Chan, GM Riedlinger, S-e Lu, KT Pham, LJ Kirstein, FG Eladoumikdachi, MA George, LB Potdevin, MJ Kowzun, SA Desai, DM Tang, CO Omene, ST Wong, L Rodriguez-Rust, S Kumar, TJ Kearney, C Liu, S Ganesan, DL Toppmeyer, KM Hirshfield; Abstract P1-15-14: Neoadjuvant liposomal doxorubicin and carboplatin is effective and tolerable for the treatment of triple negative breast cancer. Copyright 2022 by the American Association for Cancer Research. Almost half (48%) of the patients had previous antiangiogenic treatment, the most common being prior bevacizumab in 41%. The most common toxicities during DOX+CAR were grade 1 nausea in 19 pts (53%), grade 3/4 neutropenia occurred in 10 pts (28%); these pts received GCSF support with subsequent cycles; febrile neutropenia occurred in 1 pt (3%) in this group. These are very strong data with robust evidence that CD-BEV is better than CG-BEV, said invited discussant Sandro Pignata, MD, PhD, from the Istituto Nazionale Tumori di Napoli in Italy. All rights reserved. Pfisterer J, Dean AP, Baumann K, et al. Post-chemotherapy PDX is feasible and may help identify targeted approaches for patients with resistant disease. Only 6 pts (17%) had grade 1 alopecia. Cancer Res 15 February 2019; 79 (4_Supplement): P11514. This site uses cookies. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX.

These results warrant further evaluation of this combination for early stage TNBC. Conclusion: Neoadjuvant DOX+CAR demonstrated good efficacy and tolerability. There was also a trend toward an improvement in median overall survival (OS) with CD-BEV compared with CG-BEV that did not achieve significance (33.5 vs 28.2 months; HR, 0.833; 95% CI, 0.680-1.022; stratified log-rankP= .0787). All rights reserved. Cardiac safety of the combination was assessed. Of the 32 pts who completed surgery, 34% (11) achieved pCR and 64% (23) had clinical response on serial physical exam. The CD-BEV regimen has proven to be superior to carboplatin/gemcitabine/bevacizumab, carboplatin/paclitaxel, and carboplatin/paclitaxel for the treatment of recurrent ovarian cancer or in the first-line setting, but data on alopecia and hematologic toxicity are still needed when comparing these regimens, he said. CD-BEV is a new treatment option for patients with recurrent ovarian cancer suitable for platinum-based retreatment, even after previous antiangiogenic treatment, said Pfisterer, from the Gynecologic Oncology Center in Kiel, Germany. Bevacizumab maintenance, at 15 mg/kg, was continued every 3 weeks until progression of disease or unacceptable toxicities in both arms. Search for other works by this author on: 2019 American Association for Cancer Research. As of July 10, 2018, bevacizumab was ongoing in 3% of patients and 32% were alive and still being followed. Almost all (97.7%) of the patients suffered an adverse event (AE); 9.2% overall had a serious AE, the rate of which was similar between arms, and 44.6% of the grade 3-5 AEs were of special interest. TP53 (93%), PI3K/PTEN (26.6%), and NOTCH (20%) were the most commonly altered pathways. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-14. Neoadjuvant liposomal doxorubicin and carboplatin is effective and tolerable for the treatment of triple negative breast cancer [abstract]. The PFS advantage conferred by CD-BEV was also evident in subgroups examined according to platinum-free interval, the presence or absence of residual tumor, and whether patients were previously treated with antiangiogenic therapy. Most histologies were invasive ductal but included apocrine, pleomorphic lobular, and metaplastic subtypes. There were no delays in treatment due to cardiotoxicity or complications from surgical healing. Presented at: 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. At 2 years, there were 2 distant and 1 local recurrence. Background: The use of neoadjuvant platinum with taxane for triple negative breast cancer (TNBC) has gained increased attention for improving rates of pathologic complete response (pCR). Another weakness is thatBRCAand homologous recombination deficiency (HRD) statuses were not known in the trial, said Pignata. Three-fourths (76%) of patients had residual tumor at enrollment. The primary tumor type was epithelial ovarian cancer in 88%. 2022 MJH Life Sciences , Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways.

As an add-on to bevacizumab, carboplatin plus pegylated liposomal doxorubicin significantly extended progression-free survival compared with carboplatin and gemcitabine in patients with recurrent ovarian cancer whose first disease recurrence was >6 months after first-line platinum-based chemotherapy. For these reasons,BRCAand HRD statuses need to be investigated as possible biomarkers in clinical trials of ovarian cancer. There was high participation by under-represented groups: 23% African American, 20% Asian, 14% Hispanic. Median patient age was 62 years (range, 23-85); 62% had an ECOG performance status of 0 at baseline. The platinum-free interval was 6 to 12 months in 31% and >12 months in 69%. The mean relative dose intensity of bevacizumab was 91.5%, at 92.2% (CG-BEV) and 85.3% (CD-BEV) in the chemotherapy phase of the trial and about 96% in both arms in the maintenance phase. In an exploratory subgroup analysis for PFS, the benefit of CD-BEV was maintained whether patients had a platinum-free interval of 6 to 12 months (HR, 0.798) or >12 months (HR, 0.812), whether patients had residual tumor (HR, 0.841) or not (HR, 0.682), and whether they received antiangiogenic treatment previously (HR, 0.732) or not (HR, 0.881). Methods: A phase II single arm trial was conducted for patients (pts) diagnosed with stage II-III TNBC. Carboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs. carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. American Association for Cancer Research. Results: From 2/2015 to 5/2018, 36 pts were enrolled and 32 completed treatment; 4 pts await definitive surgery; 12 (33%) are two years from diagnosis. A prospective randomized phase III ENGOT/GCIG-Intergroup study (AGO Study Group, AGO-Austria, ANZGOG, GINECO, SGCTG). In a prospective phase III study that included nearly 700 patients, the median PFS reached 13.3 months (95% CI, 11.7-14.3) in patients randomized to CD-BEV compared with a median of 11.7 months (95% CI, 11.1-12.8) in the arm randomized to CG-BEV, reported Jacobus Pfisterer, MD, PhD, at the 2018 ESMO Congress.1The 1.6 months of improvement in median PFS in the CD-BEV arm translated to a hazard ratio of 0.807 (95% CI, 0.681-0.956; stratified log-rankP= .0128). Grade 3 neutropenia was more common in the CG-BEV arm versus CD-BEV (22.2% vs 12.0%, respectively) while grade 3 hypertension occurred in 27.7% of the CD-BEV group versus 20.7% of the CG-BEV arm.

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