Indirect treatment comparison of olaparib and talazoparib in germline BRCA-mutated HER2-negative metastatic breast cancer

2021 ◽  
Author(s):  
Charles McCrea ◽  
Robert Hettle ◽  
Poonam Gulati ◽  
Ankush Taneja ◽  
Preety Rajora
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Fixed Effects ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Significant Difference ◽  
Indirect Treatment

Aim: Two poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib are approved for patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer. Methods: A Bayesian fixed-effects indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy (primary outcome of progression-free survival [PFS]) and safety of PARP inhibitor monotherapy. Results: ITC of data from the OlympiAD (olaparib) and EMBRACA (talazoparib) studies suggested no significant difference in efficacy (PFS) between olaparib and talazoparib. However, there were differences in specific adverse events; patients receiving olaparib had a higher rate of nausea and vomiting, while those receiving talazoparib had a higher rate of alopecia and anemia. Discussion: These data support the benefit of the PARP inhibitor class in gBRCAm HER2-negative metastatic breast cancer.

Indirect treatment comparison of the efficacy and safety of olaparib 300 mg tablets BID and talazoparib 1 mg once daily in the treatment of patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12570-e12570 ◽  
Author(s):  
Charles McCrea ◽  
Robert Hettle
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Nausea And Vomiting ◽  
Efficacy And Safety ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Increased Risk ◽  
Significant Difference ◽  
Indirect Treatment

e12570 Background: PARP inhibitor treatment with olaparib or talazoparib has been shown to improve progression-free survival (PFS) versus chemotherapy treatment of physician’s choice in patients with germline BRCA-mutated (gBRCA) HER2-negative metastatic breast cancer. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) analysis was performed to simulate the comparative efficacy and safety of alternative PARP treatment in this setting. Methods: Bayesian fixed effects ITCs of data published for OlympiAD (NCT02000622) and EMBRACA (NCT01945775) was conducted using the gemtc package in R. Efficacy analyses were performed on the primary endpoint of PFS by blinded independent central review. Safety analyses included the odds ratio (OR) of adverse event (AE)-related discontinuations, and common AEs of any grade reported in each study. All analyses compared olaparib with talazoparib. Results: Efficacy analyses show no significant difference in PFS across treatments (PFS hazard ratio of 1.09, 95% credible interval [0.72; 1.65]). Safety analyses predict differences in AEs across PARP treatment, including hematological events, alopecia, nausea and vomiting (Table). No difference in AE-related discontinuations was observed (0.93 [0.25–3.42]). Conclusions: Results of the ITC suggest that olaparib and talazoparib are equally efficacious on PFS, and differ in AE risk profile, with olaparib predicted to have fewer common hematological and alopecia events, but an increased risk of nausea and vomiting versus talazoparib. Observed differences require confirmation in comparative studies. Limitations of the analysis include heterogeneity in study design, reporting of AEs, and mix of chemotherapies used in the control arm of the studies. [Table: see text]

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

Systematic review and meta-analysis of post-progression outcomes in ER+/HER2- metastatic breast cancer after treatment with endocrine therapy and CDK 4/6 inhibitors within randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1059-1059
Author(s):  
Elisabetta Munzone ◽  
Eleonora Pagan ◽  
Vincenzo Bagnardi ◽  
Emilia Montagna ◽  
Giuseppe Cancello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival

1059 Background: CDK4/6 inhibitors combined with endocrine therapy (ET) deeply transformed the treatment landscape of HR+/HER2− advanced breast cancer. After progression with the combination, there are no established guidelines for an optimal sequencing of the various therapeutic options. Data from randomized clinical trials (RCT) suggest that subsequent progression free survival (PFS2) was not compromised by the use of these drugs and time to subsequent chemotherapy (TTC) may be delayed. Therefore, we performed a meta-analysis to evaluate the benefit of such treatments on PFS2 and on delaying the TTC. Methods: We conducted a systematic literature search using PubMed to select all available randomized clinical trials of CDK4/6-inhibitors and ET reporting PFS2 or TTC data in first- or second-line therapy of HR+/HER2- pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC with 95% confidence intervals (CI) using fixed-effects models. The pooled HRs for PFS and OS were also calculated. I2 was used to quantify heterogeneity between studies’ results. Results: Seven studies (PALOMA 1-2-3, MONALEESA 3-7, MONARCH 2-3) were included in our analyses (n = 3912 patients). A clear PFS2 benefit was observed in patients who received CDK 4/6 inhibitors + ET (pooled HR = 0.67, 95% CI = 0.61 to 0.74, I2 = 0.0%) and also a delay in subsequent TTC (pooled HR = 0.63, 95% CI = 0.58 to 0.70, I2 = 0.0%). As previously reported, the benefit in terms of PFS (pooled HR = 0.54, 95% CI = 0.50 to 0.59, I2= 0%) and OS (pooled HR = 0.77, 95% CI = 0.68 to 0.86, I2= 0%) was also confirmed. Conclusions: CDK4/6-inhibitors plus ET compared with ET alone improve PFS2, and TTC. The delay of chemotherapy can spare the patients toxicities, potentially improving the quality of life. Thus, the observed benefit in PFS2 may postpone the onset of endocrine resistance and may offer an additional therapeutic advantage in this setting.

Fulvestrant versus everolimus plus exemestane for patients with metastatic breast cancer resistant to aromatase inhibitors: Clinical experience from real world.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12522-e12522
Author(s):  
Yi Li ◽  
Yizhao Xie ◽  
Yannan Zhao ◽  
Xi-Chun Hu ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Propensity Score ◽  
Target Therapy ◽  
Real Life ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Hormone Receptor Positive ◽  
Significant Difference

e12522 Background: To present treatment patterns and the outcome of pure endocrine therapy fulvestrant (FUL) versus Exemestane (EXE)and target therapy everolimus (EVE) combination among hormone receptor-positive (HR+)/human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) after progression on aromatase inhibitor (AI) in the real-life setting. Methods: Patients with HR+/HER2- MBC after AI who received FUL or EVE-EXE between June 2013 and June 2016 were identified from electronic database. Outcome measures included progression free survival (PFS), overall survival (OS) and safety profile. Propensity score matching (PSM) was applied to minimize potential confounders. Results: Among the 168 patients included, 124 patients received FUL and 44 patients treated with EVE-EXE. Patients that received EVE-EXE were significantly younger, more likely to have visceral, liver, multiple sites of metastases and had received more prior chemotherapy than FUL group. There was no significant difference in PFS after adjusted for propensity score between two groups (HR,1.173; 95%CI, 0.797-1.727; p = 0.419). In subgroup analysis, treatment effects were consistent across predefined subgroups except for the subgroup of multiple metastatic sites which the median PFS was significantly longer in EVE-EXE group than in FUL group (6.1vs3.2months, respectively; HR = 0.508;95%CI,0.299-0.862; p = 0.012). The toxicity of FUL regimen was more manageable. More patients discontinued the treatment due to intolerable toxicity in EVE-EXE group than FUL group. Conclusions: We observed substantial changes in treatment patterns in patients received EVE-EXE and FUL. Treatment outcomes were comparable between two schedules after adjusted for confounding factors, while FUL has been better tolerated. Clinical trial information: NCT03695341.

Lack of Benefit of Maintenance Paclitaxel in First-Line Chemotherapy in Metastatic Breast Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3912-3918 ◽  
Author(s):  
Alessandra Gennari ◽  
Dino Amadori ◽  
Mario De Lena ◽  
Oriana Nanni ◽  
Paolo Bruzzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Chemotherapy ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
First Line ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Significant Difference

Purpose This randomized study compared maintenance paclitaxel with control in metastatic breast cancer patients not experiencing progression after first-line anthracycline/paclitaxel combination chemotherapy. Methods Between April 1998 and October 2003, 459 metastatic breast cancer patients received first-line combination chemotherapy with epirubicin or doxorubicin plus paclitaxel. Of these, 255 who had a response or stable disease were then randomly assigned onto the Maintenance Paclitaxel 1 (MANTA1) study, comparing eight courses of maintenance paclitaxel versus control (ie, no additional chemotherapy administration). The primary end point was progression-free survival. Results The study was prematurely concluded after a futility analysis, which was performed on 215 of the 238 patients randomly assigned within December 2002. Of these, 109 patients were assigned to maintenance paclitaxel and 106 were assigned to stopping chemotherapy. No significant difference in median progression-free survival was observed (8.0 months for maintenance paclitaxel and 9.0 months for control). There was no significant difference in median survival time (28.0 v 29.0 months). When the Bayesian method for monitoring clinical trials was applied to these data, even under an enthusiastic prior distribution, in the posterior distribution there was only an 8.6% chance of observing a 3-month improvement in median progression-free survival in the group receiving maintenance paclitaxel. After these results study accrual was closed. Conclusion Compared with control, the administration of additional courses of paclitaxel in patients who achieve disease control after six to eight courses of first-line anthracycline plus paclitaxel combination chemotherapy does not improve progression-free survival.

Conventional versus cytokinetic polychemotherapy with estrogenic recruitment in metastatic breast cancer: results of a randomized cooperative trial.

1987 ◽  
Vol 5 (3) ◽  
pp. 339-347 ◽  
Author(s):  
P F Conte ◽  
P Pronzato ◽  
A Rubagotti ◽  
A Alama ◽  
D Amadori ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Statistical Significance ◽  
Objective Response ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Free Survival ◽  
Significant Prolongation ◽  
Significant Difference

Diethylstilbestrol (DES) can induce a recruitment into the proliferative pool of previously resting breast cancer cells in vivo. In order to verify if estrogenic recruitment could result in a larger tumor cell killing by chemotherapy, 117 patients with metastatic breast cancer were randomized to receive CEF (cyclophosphamide, 600 mg/m2; epidoxorubicin, 60 mg/m2; and 5-fluorouracil, 600 mg/m2 on day 1); DES-CEF (cyclophosphamide, 600 mg/m2 on day 1; DES, 1 mg orally on days 5, 6, and 7; and epidoxorubicin, 60 mg/m2, and 5-fluorouracil, 600 mg/m2, on day 8) every 21 days. No significant difference in objective response rates, survival, or progression-free survival was seen between the two regimens. Patients in the DES-CEF arm experienced a higher complete response (CR) rate (24.1% v 16.1%), which reached statistical significance in the case of soft-tissue metastasis (48% v 27.3%; P less than .05) and estrogen receptor-negative tumors (35.7% v 11.1%; P less than .025). Survival and progression-free survival of patients refractory to treatment were not worsened by estrogenic recruitment. In the subset of patients failing after adjuvant polychemotherapy, DES-CEF unexpectedly induced a significantly longer survival (greater than 802 days v 375 days; P = .029) and progression-free survival (239 days v 192 days; P = .041) than CEF. The DES-CEF regimen was more myelotoxic, and 43.3% of the DES-CEF cycles had to be delayed because of leukopenia in comparison with 11.8% of the CEF cycles (P less than .0001). In conclusion, chemotherapy with estrogenic recruitment was able to induce more CRs in certain subsets of patients and a significant prolongation in survival and progression-free survival of patients failing after adjuvant polychemotherapy. These results have been achieved despite a significantly lower dose intensity of chemotherapy.

scholarly journals Randomised Phase 2 study of lapatinib and vinorelbine vs vinorelbine in patients with HER2 + metastatic breast cancer after lapatinib and trastuzumab treatment (KCSG BR11-16)

2019 ◽  
Vol 121 (12) ◽  
pp. 985-990 ◽  
Author(s):  
Sung Hoon Sim ◽  
In Hae Park ◽  
Kyung Hae Jung ◽  
Sung-Bae Kim ◽  
Jin-Hee Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Median Number ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Phase 2 Study ◽  
Significant Difference ◽  
Clinical Benefits

Abstract Background The continuum of anti-HER2 agents is a standard treatment of HER2 + metastatic breast cancer (MBC). This study evaluated the efficacy of lapatinib plus vinorelbine in patients progressed on both trastuzumab and lapatinib treatments. Methods A total of 149 patients were randomly assigned to lapatinib with vinorelbine (LV) (n = 75; lapatinib, 1000 mg daily; vinorelbine 20 mg/m2 D1, D8 q3w) or vinorelbine (V) (n = 74; 30 mg/m2 D1, D8 q3w). The primary endpoint was progression-free survival (PFS) rate at 18 weeks. Results The median number of previous anti-HER2 therapies was 2 (range 2–5). There was no significant difference in PFS rate at 18 weeks between LV and V arms (45.9% vs 38.9%, p = 0.40). ORR was 19.7% in LV arm, and 16.9% in V arm (p = 0.88). PFS and OS did not differ between two arms (LV vs V; median PFS, 16 vs 12 weeks, HR = 0.86, 95% CI 0.61–1.22; median OS, 15.0 vs 18.9 months, HR = 1.07, 95% CI 0.72–1.58). Toxicity profiles were similar in both arms and all were manageable. Conclusions Lapatinib plus vinorelbine treatment was tolerable; however, it failed to demonstrate the clinical benefits over vinorelbine alone in patients with HER2 + MBC after progression on both trastuzumab and lapatinib. Clinical trial registration ClinicalTrials.gov number NCT01730677.

scholarly journals A multicenter analysis of treatment patterns and clinical outcomes of subsequent therapies after progression on palbociclib in HR+/HER2− metastatic breast cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110228
Author(s):  
Yi Li ◽  
Wei Li ◽  
Chengcheng Gong ◽  
Yabin Zheng ◽  
Quchang Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Treatment Options ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Subsequent Treatment ◽  
Significant Difference

Introduction: Endocrine therapy and cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) are standard treatment options for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2–) metastatic breast cancer (MBC). However, the efficacy of standard subsequent therapies after CDK4/6i-based treatment is unclear. This study aimed to examine physician practice patterns and treatment outcomes of subsequent therapies administered after progression on palbociclib therapy in clinical practice. Methods: The study included 200 patients with HR+/HER2– MBC who underwent subsequent treatments after progressing on palbociclib-based regimens in five Chinese institutions between August 2017 and April 2020. The treatment pattern, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were reported. Results: A total of 200 patients were included, of whom 147 (73.5%) and 53 (26.5%) received subsequent chemotherapy and endocrine therapy, respectively. The frequently used monochemotherapy regimens were taxane ( n = 29), capecitabine ( n = 21), and vinorelbine ( n = 17), while the endocrine therapy regimens were chidamide plus exemestane ( n = 16) and everolimus plus exemestane ( n = 9). The overall median PFS (mPFS) was 5.5 months, with no significant difference in mPFS between the chemotherapy and endocrine therapy groups ( p = 0.669). However, among patients not sensitive to prior palbociclib treatment, those administered chemotherapy had significantly longer PFS than those administered endocrine therapy ( p = 0.006). The mPFS with endocrine therapy after first-, second-, and subsequent-line palbociclib was 13.4, 3.1, and 4.1 months, respectively ( p = 0.233); in contrast, the mPFS with chemotherapy was 7.2, 6.5, and 4.9 months after first-, second-, and subsequent-line palbociclib, respectively ( p = 0.364). The median OS was not achieved. The ORR was 10.6% among the 198 patients included in the analysis. Conclusions: Physicians prefer chemotherapy over endocrine therapy for the treatment of patients with HR+/HER2– MBC who develop progression on palbociclib. Sensitivity to previous palbociclib treatment might be one of the indicators for predicting response to subsequent treatment. ClinicalTrials.gov identifier: NCT04517318

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