Cisplatin chemotherapy in the treatment of BRCA1-positive metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1099-1099 ◽  
Author(s):  
T. Byrski ◽  
M. Foszczynska-Kloda ◽  
T. Huzarski ◽  
R. Dent ◽  
J. Gronwald ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Brca1 Mutation ◽  
Performance Status ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Institutional Review Boards ◽  
Prior History ◽  
Significant Activity ◽  
Metastatic Setting

1099 Background: Preclinical data suggest that women with BRCA1 related breast cancers may be particularly sensitive to chemotherapeutic agents that cause DNA damage such as cisplatin chemotherapy. This study was conducted to assess the efficacy and safety of cisplatin chemotherapy in patients with BRCA1 positive MBC. Methods: This was a multicenter, open label, single arm study of cisplatin 75 mg/m2 given intravenously every three weeks until disease progression or toxicity. The primary objective was to assess antitumour activity of cisplatin, as measured by clinical benefit response (CR, PR, or SD ≥ 6 months). Eligible patients had locally recurrent or MBC, had 0–2 prior chemotherapy regimens in the metastatic setting, and had received prior therapy with an anthracycline. Patients were restaged every eight weeks. The study protocol was approved by the institutional review boards of participating institutions. Results: A total of 15 patients were enrolled. Mean age was 48.1 years (range: 32 to 70). ECOG performance status scores were 0 (6 pts), 1 (5 pts), 2 (4 pts). All patients had a confirmed BRCA1 mutation (7 with C61G mutation, 7 with 5382 insC, 1 with 4153delA). Five patients (33%) were ER or PR + and none were HER-2+. Prior history of MBC chemotherapy included 1 regimen (4 pts) and 2 regimens (7 pts). Seven (46%) and 4 (26%) patients had complete and partial responses by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, for an overall response rate of 72%. Median duration of response has not yet been reached. In general, cisplatin was well tolerated. Neutropenia was the commonest toxicity with 33% grade 2 (6,7% and 0%, grades 3 and 4 neutropenia). No patients developed febrile neutropenia. Conclusions: Significant activity and favorable toxicity profile provides a basis for considering cisplatin for further evaluation in phase III trials for women with BRCA1 positive MBC. No significant financial relationships to disclose.

Impact of eribulin on overall survival in patients with metastatic breast cancer with visceral disease.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 239-239
Author(s):  
L. T. Vahdat ◽  
J. Cortes ◽  
C. Twelves ◽  
J. Wanders ◽  
S. Seegobin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Number Of Patients ◽  
Metastatic Setting ◽  
To Receive ◽  
Visceral Disease

239 Background: Visceral disease is associated with poor survival outcome in women with metastatic breast cancer (mBC). Eribulin mesylate is a nontaxane microtubule dynamics inhibitor indicated for 3rd-line monotherapy in patients (pts) with mBC previously treated with at least two chemotherapeutic regimens in the metastatic setting, including an anthracycline and a taxane. Methods: Evidence from the global, randomized, multicenter, phase III clinical trial of eribulin in mBC (EMBRACE) demonstrated improved overall survival (OS) for eribulin-treated pts when compared to treatment of physician’s choice (TPC). In this unplanned subgroup analysis, we compare the clinical benefit of eribulin to TPC in mBC pts with visceral disease using the Independent Review database. Patients were categorized as having visceral disease if they had target or non-target lesion involvement in the adrenal gland, liver, lung, pleural, pericardial/peritoneal cavity, spleen, or thyroid. Patients with brain metastases were excluded from the trial. Results: EMBRACE enrolled 762 pts with mBC, with single organ disease present in 120 pts (15.7%). The remaining pts had multi-organ disease. A total of 81.9% (624) of pts were classified as having visceral disease–81.3% (413) randomized to receive eribulin and 83.1% (211) to receive TPC. Metastatic tumor site was similar in eribulin and TPC arms, with liver (58.3%; 62.6%), lung (38.8%; 37.4%) and pleural (17.1%; 16.5%) involvement. Patients with visceral disease treated with eribulin demonstrated a significant benefit in OS compared to TPC (HR 0.77, p=0.02). Median OS in mBC pts with visceral disease was 12.45 months (mos) for eribulin-treated pts, with ORR=11.0% and CBR*=21.7% compared to OS=10.12 mos, ORR=5.0%, CBR*=16.6% for TPC-treated patients (*CBR defined as CR+PR+SD>6mos). No significant treatment difference was observed in the non-visceral disease patients however due to the small number of patients with non-visceral disease, no robust statistical conclusions can be made. Conclusions: Treatment with eribulin resulted in significant improvement in overall survival for mBC pts with visceral disease compared to other commonly used chemotherapeutic agents.

BOLERO-2: Health-related quality-of-life (HRQoL) in metastatic breast cancer patients treated with everolimus and exemestane versus exemestane.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 125-125 ◽  
Author(s):  
Hope S. Rugo ◽  
J. Thaddeus Beck ◽  
José Baselga ◽  
Shinzaburo Noguchi ◽  
Michael Gnant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Metastatic Breast ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Rank Test ◽  
Breast Cancer Patients

125 Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) + exemestane (EXE) or EXE + placebo. A preplanned 12-mo median time interim analysis demonstrated that EVE + EXE significantly improved progression-free survival (PFS) vs EXE + placebo, but EVE + EXE resulted in a higher rate of grade 3-4 toxicity. Per-protocol patients reported HRQoL data are limited; here we report on additional post hoc analyses of these outcomes. Methods: Using the EORTC QLQ-C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. QLQ-C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS), where higher scores (range, 0-100) indicate better HRQoL. Analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ-C30 score relative to baseline. Treatment arms were compared using a stratified log-rank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score, ECOG performance status, prognostic risk factors, and treatment history. Results: Baseline QLQ-C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference –0.7 [95% CI, –4.3-3.0]). Median TTD in HRQoL was 7.0 mo (95% CI, 5.6-8.3) for EVE + EXE vs 5.6 (95% CI, 4.2-7.0) for EXE (p = .0792). Adjusted HR (0.80) approached significance (95% CI, 0.63-1.02). At the 10-point MID, median TTD for EVE + EXE was 9.7 mo (95% CI, 8.3-11.2) vs 8.4 mo (95% CI, 6.3-12.5) for EXE. Adjusted HR was 0.90 (95% CI, 0.69-1.18). Conclusions: These additional analyses from the BOLERO-2 study demonstrate that in addition to significantly improving PFS, EVE + EXE does not compromise HRQoL.

CanStem111P trial: A phase III study of napabucasin (BBI-608) plus nab-paclitaxel (nab-PTX) with gemcitabine (gem) in adult patients with metastatic pancreatic adenocarcinoma (mPDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4148-TPS4148 ◽  
Author(s):  
Tanios S. Bekaii-Saab ◽  
Chung-Pin Li ◽  
Takuji Okusaka ◽  
Bert H. O'Neil ◽  
Michele Reni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Disease Control ◽  
Performance Status ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Study Population

TPS4148 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutic agents, including nab-PTX and gem. Encouraging anticancer activity in mPDAC was observed in a phase Ib (El-Rayes et al, ASCO 2016) study of 37 pts, reporting 93% (28/30) disease control rate (DCR) and 50% (15/30) overall response rate (ORR), with 1 complete and 14 partial responses and prolonged disease control ( > 24 wks) in 57% (17/30) of pts who have had a RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia and Asia. Methods: This study (ClinicalTrials.gov NCT02993731) will assess the efficacy of napabucasin+nab-PTX+gem vs nab-PTX+gem in pts with mPDAC (n = 1132). Pts must have been diagnosed with mPDAC < 6 weeks prior to randomization and not have received treatment for metastatic disease. Pts are randomized in a 1:1 ratio to receive napabucasin 240 mg PO twice daily continuously plus nab-PTX+gem IV weekly for 3 out every 4 weeks, or nab-PTX+gem IV weekly for 3 out every 4 weeks. Pts will be stratified by geography, performance status and presence of liver metastases. Treatment will continue until disease progression, death, intolerability or patient/investigator decision to stop. Primary endpoint is overall survival (OS) in the general study population (HR 0.80 for OS improvement from 8.5 to 10.63 months); secondary endpoints include progression free survival (PFS), OS and PFS in the biomarker positive sub-population, ORR and DCR, safety and quality of life. In addition, blood and tumor archival tissue will be assessed for pharmacokinetic and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02993731.

REACHAUT: First-line (1L) ribociclib (RIB) + endocrine therapy (ET) in HR+, HER2- metastatic breast cancer (MBC) in the real-world setting.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12527-e12527
Author(s):  
Christian F. Singer ◽  
Leopold Öhler ◽  
Daniel Egle ◽  
Richard Greil ◽  
Edgar Petru ◽  
...  
Keyword(s):  
Median Duration ◽  
Real World ◽  
Performance Status ◽  
Metastatic Breast ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Minimal Impact ◽  
Real World Setting ◽  
Common Prior ◽  
Metastatic Setting

e12527 Background: RIB + aromatase inhibitor (AI) is approved as 1L treatment (tx) for HR+, HER2− MBC. Real-world data on efficacy and safety of RIB+AI are limited. REACHAUT, a prospective, noninterventional trial assessed the safety of RIB+AI in 1L setting in postmenopausal patients (pts) with HR+, HER2− MBC in a real-world setting. First interim analysis results about safety are presented. Methods: 75 postmenopausal pts with HR+, HER2− MBC, QTc < 450 msec, and no prior ET for advanced disease were enrolled at 13 sites. 1L chemotherapy (CT) was allowed. Results: At data cutoff (25-Jan-2019), 61 pts were evaluable for safety (ongoing, n = 44; discontinued, n = 17). Median duration of follow-up was 29 d. Median age at baseline was 65 y ( < 65 y, n = 28; ≥65 y, n = 33); ECOG performance status was 0 (n = 39) and 1 (n = 12). 42.6% had visceral (lung, liver) metastases (mets), while 34.4% had bone only mets. Most common prior tx included CT (29.5% in neoadjuvant/adjuvant/metastatic setting) and ET (41%). Pts received RIB in 1L (93.4%) and second-line (6.6%) setting. In 80.3% pts receiving RIB, the ET partner included letrozole (57.4%), exemestane (11.5%), anastrozole (9.8%). Median duration of RIB exposure was 100 d. Median time to first AE was 14 d. 83.6% pts experienced AEs with mild (63.9%) to moderate (50.8%) severity. Serious AEs were noted in 6.6% pts. Most common AEs were neutropenia (42.6%) and QTc prolongation (24.6%). 4.9% pts had hepatobiliary AEs. Due to AEs, dose adjustments (4.9%) and dose interruptions (19.8%) were needed. No deaths were reported; median PFS was not reached. Subgroup analysis by age ( < 65 y vs ≥65 y) showed that the incidence of AEs was 55.9% vs 44.1%. Neutropenia was reported in 46.4% pts aged < 65 y vs 39.3% pts aged ≥65 y; QT prolongation events were noted in 21.4% pts aged < 65 y vs 27.2% pts aged ≥65 y. Dose adjustments and dose interruptions were needed in 14.3% and 46.4% pts aged < 65 y vs 15.2% and 45.5% pts aged ≥65 y. Conclusions: Overall safety of RIB+AI in routine clinical practice in REACHAUT was consistent with that reported in the MONALEESA-2 study. In real-world setting, pt age ( < 65 y vs ≥65 y) had minimal impact on AEs. Clinical trial information: NIS006622.

Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.

1988 ◽  
Vol 6 (7) ◽  
pp. 1098-1106 ◽  
Author(s):  
H B Muss ◽  
H B Wells ◽  
E H Paschold ◽  
W R Black ◽  
M R Cooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Metastatic Breast ◽  
Megestrol Acetate ◽  
Phase Iii ◽  
Bone Lesions ◽  
Similar Response ◽  
Time To Progression ◽  
Adjusted Analysis

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.

Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10730-10730
Author(s):  
D. R. Fescina ◽  
W. Gradishar ◽  
M. Orlando ◽  
J. Rubinsak ◽  
L. Haney ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line Therapy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

10730 Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company. [Table: see text]

A phase III, open-label, randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes: Subgroup analyses.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1049-1049 ◽  
Author(s):  
Peter Andrew Kaufman ◽  
Javier Cortes ◽  
Ahmad Awada ◽  
Louise Yelle ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Randomized Study ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Her2 Status ◽  
Open Label ◽  
Eribulin Mesylate ◽  
Prior Chemotherapy ◽  
Metastatic Setting ◽  
Subgroup Analyses

1049^ Background: This phase III study, comparing eribulin versus capecitabine, showed a non-significant trend for superior overall survival (OS; hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.77, 1.00]; p = 0.056) but not progression-free survival (PFS; HR 1.08 [95% CI 0.93, 1.25]; p = 0.31). Pre-specified exploratory subgroup analyses previously presented showed that patients with triple-negative, ER-negative or HER2-negative disease may have a greater benefit in OS with eribulin compared with capecitabine. Here we present further pre-specified exploratory analyses of OS and PFS. Methods: Patients (eribulin n=554; capecitabine n=548) with locally advanced or MBC had received ≤3 prior chemotherapy regimens (≤2 for advanced disease), including an anthracycline and a taxane. Patients were randomized (stratified for geographic region and HER2 status) 1:1 to 21-day cycles of eribulin mesylate 1.4 mg/m2 i.v. on days 1 and 8 or capecitabine 1.25 g/m2BID orally on days 1-14. Further pre-specified exploratory subgroups included: age; receptor status; number and setting of prior chemotherapy regimen(s); sites of disease; number of organs involved; and time to progression after last chemotherapy. Results: From analyses for OS, patients with only non-visceral disease (HR 0.51; 95% CI 0.33, 0.80), with >2 organs involved (HR 0.75; 95% CI 0.62, 0.90), who had progressed >6 months after last chemotherapy (HR 0.70; 95% CI 0.52, 0.95), or who had received an anthracycline and/or a taxane in the metastatic setting (HR 0.84; 95% CI 0.72, 0.98), appeared to benefit more from treatment with eribulin compared with capecitabine. For OS, in no subgroup was a trend favoring capecitabine seen. Data for other pre-specified subgroups for both OS and PFS will be presented. Conclusions: In addition to patients with triple-, ER-, or HER2-negative disease, further pre-specified exploratory analyses suggest that other patient subgroups may particularly benefit from treatment with eribulin; further studies are warranted to address these hypotheses. Clinical trial information: NCT00337103.

Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281.

1995 ◽  
Vol 13 (6) ◽  
pp. 1443-1452 ◽  
Author(s):  
J Aisner ◽  
C Cirrincione ◽  
M Perloff ◽  
M Perry ◽  
D Budman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Initial Therapy ◽  
Phase Iii ◽  
Survival Times ◽  
Improve Response Rate ◽  
Group B ◽  
Leukemia Group

PURPOSE We sought to compare three doxorubicin-based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. MATERIALS AND METHODS Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status < or = 2, and provided informed consent were eligible. Treatment included the following: arm I--cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II--vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III--VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. RESULTS Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm III when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively. Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade > or = 3 toxicities on arm II than I, and most occurred on arm III (P = .02). CONCLUSION The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed.

Overall survival in patients with breast cancer treated with a CDK 4/6 inhibitor plus fulvestrant: A U.S. Food and Drug Administration pooled analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1055-1055
Author(s):  
Jennifer J Gao ◽  
Joyce Cheng ◽  
Tatiana Michelle Prowell ◽  
Erik Bloomquist ◽  
Shenghui Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Endocrine Therapy ◽  
Cox Regression ◽  
De Novo ◽  
Small Sample Size ◽  
Performance Status ◽  
Metastatic Breast ◽  
Small Sample ◽  
Phase Iii

1055 JJG, JC, TMP contributed equally. JAB, LAK contributed equally. Background: Cyclin dependent kinase 4/6 inhibitors (CDKIs) are oral targeted agents approved for use in combination with endocrine therapy as first or secondline treatment of hormone-receptor positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. We previously reported the pooled analyses of progression-free survival of patients in certain clinicopathologic subgroups, and results showed a consistent benefit from the addition of a CDKI to endocrine therapy. Here, we report the pooled overall survival (OS) results in patients treated with a CDKI plus fulvestrant. Methods: We pooled individual patient data (n=1948) from three phase III randomized breast cancer trials of a CDKI plus fulvestrant submitted to the FDA in support of marketing applications. All analyzed patients received at least one dose of a CDKI or placebo, plus fulvestrant. The median OS was estimated using Kaplan-Meier (KM) methods, and hazard ratios (HR) with corresponding 95% confidence intervals (CIs) were estimated using Cox regression models. Results: Results of OS analyses, including all pooled patients, patients treated in the first-line setting, and patients treated in the second line and later settings, are summarized in the table below. Additional subgroup analyses of OS by progesterone receptor status, site of metastases, breast cancer histology, ECOG performance status, race, and de novo metastatic presentation all favored adding a CDKI to fulvestrant. In patients age < 40, the estimated OS HR favored fulvestrant alone, but this subgroup had a small sample size (n=89), so this result must be interpreted with caution. All results are considered exploratory and hypothesis-generating. Conclusions: Addition of CDKIs to fulvestrant appears to confer a consistent survival benefit across all pooled patients and within most clinicopathological subgroups of interest.[Table: see text]

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