Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1115-TPS1115 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Lorenzo Trippa ◽  
Paulina Lange ◽  
Chelsea Andrews ◽  
Heather L. McArthur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Breast Cancer Patients ◽  
Open Label ◽  
True Response ◽  
Tumor Mutational Burden

TPS1115 Background: A previous study from our group showed that approximately 9% of metastatic breast cancer (MBC) is hypermutated, defined as a tumor mutational burden (TMB) ≥10 Mutations/Megabase (Mut/Mb). The aim of this study is to evaluate if patients with hypermutated HER2-negative MBC benefit from the combination of nivolumab plus ipilimumab. Methods: This is an open-label, single-arm, multicenter, phase 2 study assessing the efficacy of nivolumab 3 mg/Kg intravenously (IV) every 14 days plus Ipilimumab 1 mg/Kg IV every 6 weeks in subjects with hypermutated metastatic HER2-negative breast cancer. Patients with measurable HER2-negative MBC, TMB ≥10 Mut/Mb assessed by a cancer-gene panel evaluating > 300 genes and performed in a CLIA-certified laboratory, and 0-3 prior lines of chemotherapy in the advanced setting are eligible. The primary objective is overall response rate according to RECIST 1.1. Secondary objectives include the safety and tolerability of the combination, progression-free survival, and overall survival. The study will follow a two-stage design. In the first stage 14 patients will be enrolled. If there is at least one patient with objective response, accrual will continue to the second stage where an additional 16 patients will be enrolled. If there are at least 4 patients with an objective response among the 30 patients, the regimen will be considered worthy of further study. If the true response rate is 5%, the chance the regimen is declared worthy of further study is less than 5%. If the true response rate is 25%, the chance that the regimen is declared worthy of further study is > 90%. Tumor biopsies, peripheral blood, and stool collection are mandatory and will be obtained at baseline, on treatment (end of cycle 1), and at disease progression and will be assessed for potential biomarkers of treatment response. The trial was activated in February 2019, and accrual should be completed in 18 months. Clinical trial information: NCT03789110.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Chemotherapy ◽  
2017 ◽  
Vol 62 (5) ◽  
pp. 307-313 ◽  
Author(s):  
Jun Yamamura ◽  
Norikazu Masuda ◽  
Daigo Yamamoto ◽  
Shigeru Tsuyuki ◽  
Masahide Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival

Background: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. Methods: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. Results: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. Conclusion: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

Phase II randomized, open-label study of YM155 (sepantronium bromide) plus docetaxel versus docetaxel alone as first-line treatment for HER2 negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 548-548
Author(s):  
Michael R. Clemens ◽  
Anne Therese Keating ◽  
Oleg Gladkov ◽  
Fei Jie ◽  
Joyce Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Randomized Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Eligibility Criteria ◽  
Prior Therapy

548 Background: YM155 (YM) is a small molecule survivin suppressant. In a phase I/II study of YM plus docetaxel (D) in solid tumors evidence of anti-tumor activity was observed in women with human epidermal growth factor 2 non-overexpressing (HER2 negative) metastatic breast cancer (mBC). Methods: This was a randomized study of YM plus D versus D as 1st line treatment in subjects with HER2 negative mBC. Eligibility criteria were: ECOG < 1, no prior chemotherapy for mBC, and at least one measurable lesion. Primary endpoint was progression free survival (PFS); secondary endpoints were: objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR) and safety. YM was administered at 5 mg/m2/day as a 168 hr continuous infusion followed by 14 Day (d) observation and D was administered at 75 mg/m2over 1 hr on d1 every 21d. In the control arm, D was dosed per investigator choice q 21d. Results: 101 subjects were randomized (50 YM + D; 51 D). Median (m) age 55 (range: 25 – 79), 25% had triple negative disease, > 60% had bone and lymph mets, 86% had prior therapy for BC. mPFS (days) was 251 (95%CI: 176 – 333) YM + D vs 252 (95%CI: 202-433) D (p=0.34). ORR, CBR and TTR (YM+D; D): 26% vs. 25.5%; 82% vs. 84.3% and 45 vs 59 d. OS data are immature but showed no difference (p=0.911). Adverse events [AEs (> 25%)] [YM + D% vs D %]: neutropenia 83 vs 84, alopecia 62.5 vs 53, fatigue 50 vs 41.2, nausea 35.4 vs 41.2, leucopenia 27 vs 33 and dyspnoea 33 vs 14. Common (>10%) serious AEs [YM + D% vs D%]: febrile neutropenia 21 vs 8 and neutropenia 10 vs 8. Conclusions: Preclinical and clinical evidence suggested the combination of YM + D may offer additional benefit to D alone in subjects with mBC. This study showed no difference in efficacy, but the combination appeared to be well tolerated. Clinical trial information: NCT01038804.

Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): Results from a phase II randomized discontinuation trial (RDT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 535-535 ◽  
Author(s):  
Eric P. Winer ◽  
Sara Tolaney ◽  
Hovav Nechushtan ◽  
Raanan Berger ◽  
Razelle Kurzrock ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Bone Scan ◽  
Tumor Regression ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Bone Lesions ◽  
Respiratory Compromise ◽  
Open Label

535 Background: Dysregulation of MET and VEGF signaling has been implicated in breast cancer development and progression, including tumor invasion and dissemination. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types, including MBC. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized discontinuation phase was progression-free survival (PFS). Results: Enrollment to this cohort is complete (n = 45); all pts are unblinded. Baseline characteristics: median age 56; invasive ductal 86%, invasive lobular 7%; ER+ 93%, HER2+ 18%, triple- 5%; visceral disease 91%; bone metastases 73%; median prior lines of therapy 3 (range 1-8), including 71% with prior anthracyclines. Median follow-up was 2.9 mos (range 0.1 -16). 21 pts (47%) completed Lead-in stage with only 9 randomized to continue cabo (n = 5) or placebo (n = 4). Median PFS from Study Day 1 was 4.1 mos. At wk 12, objective response rate was 14% and disease control rate 48%. Tumor regression was observed in 25/39 pts (64%) with ≥1 post-baseline tumor assessment. 4/10 pts evaluable by bone scan had partial resolution of bone lesions. Of 12 pts receiving narcotics for bone pain, 5 pts reported improved pain and 2 pts had decreased narcotics use, per investigator. 4/14 evaluable pts (29%) with bone metastases experienced ≥50% decline in serum NTx. Most common Grade 3/4 AEs were palmar-plantar erythrodyesthesia (13%) and fatigue (11%). One related Grade 5 AE of respiratory compromise was reported during the Lead-in stage. Conclusions: Cabo demonstrated a 14% rate of objective tumor regression in heavily pretreated MBC pts. Observed effects on bone scan and pain are consistent with those seen in other malignancies. The safety profile of cabo was comparable to that seen with other VEGFR TKIs.

A multicenter phase I-II trial of weekly paclitaxel and carboplatin plus bevacizumab in women with triple-negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1045-1045
Author(s):  
Emmanouil S. Saloustros ◽  
Aristidis Polyzos ◽  
Charalampos Christophyllakis ◽  
Nikolaos K. Kentepozidis ◽  
Lampros Vamvakas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Dna Breaks ◽  
Grade 3

1045 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. The combination of carboplatin and paclitaxel administered weekly is active and well tolerated. Bevacizumab when added to paclitaxel prolonged progression-free survival in metastatic breast cancer (MBC). We investigated the activity and toxicity of paclitaxel plus carboplatin and bevacizumab in triple-negative MBC. Methods: The study’s primary objective was to estimate the objective response rate [complete (CR) + partial remission (PR)] and toxicity of the combination in women with triple negative MBC who had no prior chemotherapy for metastatic disease. The study followed the Simon's two-stage optimal design with 16 patients initially evaluated for response and toxicity and then expanding to a total of 46 patients. The null hypothesis that the objective response rate is ≤40% could be rejected if the number of CR/PR was ≥23. Paclitaxel 90mg/m2and Carboplatin AUC 2 were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. Results: 45 women with triple negative MBC have been recruited thus far. Of them, 12 were premenopausal and 27 had prior (neo-)adjuvant chemotherapy. The median cycles administered were 5 (range 1-8). Of 38 evaluable patients we observed 7 CR, 22 PR’s for an objective response rate 76%. Seven patients achieved stable disease, while two had disease progression. Median duration of response was 8.1 months with median time to progression 9.2 months. Neutropenia grade 3 and 4 was experienced by 13 and 6 patients, respectively, with one toxic death due to febrile neutropenia. Other grade 3 toxicities included anemia/neurotoxicity (n=2), thrombocytopenia/diarrhea (n=1). Conclusions: Although still ongoingthe study has achieved the primary objective of demonstrating clinical activity for weekly carboplatin and paclitaxel in combination with bevacizumab in triple negative MBC. We believe that this triplet combination merits further evaluation in this patient population for whom there is no standard treatment. Clinical trial information: NCT00691379.

Trastuzumab deruxtecan for HER2+ advanced breast cancer

2021 ◽  
Author(s):  
Jiyun Lee ◽  
Yeon Hee Park
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Antibody Drug Conjugate ◽  
Metastatic Setting ◽  
Clinical Benefits

Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody–drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo–fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.

A phase Ib study of abemaciclib in combination with pembrolizumab for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer (MBC) (NCT02779751): Interim results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1051-1051 ◽  
Author(s):  
Hope S. Rugo ◽  
Peter Kabos ◽  
Joseph Thaddeus Beck ◽  
Michael Jon Chisamore ◽  
Anwar Hossain ◽  
...  
Keyword(s):  
Partial Response ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Primary Objective ◽  
Open Label ◽  
Phase Ib ◽  
Metastatic Setting

1051 Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase (CDK)4 and 6 inhibitor, approved to treat HR+, HER2- MBC patients (pts) on a continuous twice daily dosing schedule as monotherapy or in combination with an aromatase inhibitor as initial endocrine based therapy or in combination with fulvestrant. Abemaciclib monotherapy increased tumor immunogenicity and synergized with anti-PD-1 to boost antitumor efficacy in murine models. Here we report safety and antitumor activity of abemaciclib plus pembrolizumab in HR+, HER2- MBC pts. Methods: This multicenter, nonrandomized, open-label, multi-cohort phase Ib study of abemaciclib plus pembrolizumab enrolled a cohort of endocrine resistant HR+, HER2- MBC pts who had received 1 or 2 prior chemotherapy regimens for MBC. No prior CDK4/6 inhibitor was allowed. Patients received 150mg abemaciclib orally every 12 hours plus pembrolizumab 200mg IV on day 1 every 21 days. Primary objective was to characterize safety of the abemaciclib plus pembrolizumab combination. Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 28 pts enrolled, 15 (54%) received 1 line and 10 (36%) 2 lines of prior systemic chemotherapy in the locally advanced/metastatic setting. Safety of the combination was generally consistent with known side effects of abemaciclib and pembrolizumab and was generally manageable. Grade 3/4 adverse events in >2 pts included neutropenia (8 pts/29%), AST increase (5 pts/18%), diarrhea, and ALT increase (3 pts/11% each). Eight pts had confirmed partial response (29% ORR), and disease control rate (complete response [CR]+partial response [PR]+stable disease [SD]) was 82%. Clinical benefit rate (CR+PR+SD persisting for ≥6 months) was 46%. Median PFS and OS were 8.9 months (95% CI 3.9, 11.1) and 26.3 months (95% CI 20.0, 31.0), respectively. Conclusions: Combination of abemaciclib plus pembrolizumab demonstrated a generally tolerable safety profile with numerically higher rate of transaminase elevations than reported for the individual treatments. Compared to historical data for abemaciclib monotherapy in a similar pt population, a numerically higher but not obviously different ORR, PFS, and OS was observed. Clinical trial information: NCT02779751 .

scholarly journals Phase Ib/II single-arm trial evaluating the combination of everolimus, lapatinib and capecitabine for the treatment of HER2-positive breast cancer with brain metastases (TRIO-US B-09)

2018 ◽  
Vol 10 ◽  
pp. 175883591880733 ◽  
Author(s):  
Sara Hurvitz ◽  
Rashi Singh ◽  
Brad Adams ◽  
Julie A. Taguchi ◽  
David Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Metastatic Breast ◽  
Study Drug ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis

Background: Improving outcomes for patients with human epidermal growth factor 2-positive (HER2+) central nervous system (CNS) metastases remains an unmet clinical need. This trial evaluated a novel combination of everolimus, lapatinib and capecitabine for this disease. Methods: Patients with trastuzumab-pretreated, HER2+ breast cancer brain metastasis without prior therapy with a mammalian target of rapamycin (mTOR) inhibitor were eligible. Patients received lapatinib and everolimus daily (continuously) and capecitabine twice daily (d1–14) in 21-d cycles. The primary endpoint was the 12-week CNS objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), best CNS ORR and extra-CNS ORR. Results: A total of 19 participants were enrolled and treated with ⩾1 dose of the study drug. The median age was 58.5 years, the median number of therapies for metastatic breast cancer was 2.5 (0–11). Pretrial, 74% of participants had received prior lapatinib, capecitabine or both. A total of 63% had received previous CNS radiation or surgical resection and CNS radiation. The maximum tolerated doses were lapatinib at 1000 mg, everolimus at 10 mg, and capecitabine at 1000 mg/m2. Phase II proceeded with capecitabine at 750 mg/m2 due to better tolerability. The most common grade 3/4 adverse events were mucositis (16%), diarrhea, fatigue, and hypokalemia (11% each). Of 11 participants evaluable for 12-week CNS ORR, 3 (27%) had partial response and 7 (64%) had stable disease. The best CNS ORR in eligible participants was 28% (5/18). The median PFS and OS were 6.2 and 24.2 months, respectively. Conclusions: This novel triplet combination of lapatinib, everolimus, and capecitabine is well tolerated and yielded a 27% response rate in the CNS at 12 weeks in heavily pretreated participants. Larger studies are warranted to further evaluate this regimen. Trial registration: ClinicalTrials.gov: NCT01783756. Registered 05 February 2013, https://clinicaltrials.gov/ct2/show/NCT01783756

scholarly journals Outcome of Everolimus-Based Therapy in Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression on Palbociclib

2020 ◽  
Vol 14 ◽  
pp. 117822342094486 ◽  
Author(s):  
Ajay Dhakal ◽  
Roby Antony Thomas ◽  
Ellis G Levine ◽  
Adam Brufsky ◽  
Kazuaki Takabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Optimal Sequence ◽  
Hormone Receptor Positive

Background: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors. Objective: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib. Methods: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS). Results: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%. Conclusion: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib.

scholarly journals Real-life prognosis of 5041 bone-only metastatic breast cancer patients in the multicenter national observational ESME program

2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Marion Bertho ◽  
Julien Fraisse ◽  
Anne Patsouris ◽  
Paul Cottu ◽  
Monica Arnedos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real Life ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Life Prognosis

Background: Bone-only (BO) metastatic breast cancer (MBC) is considered a more favorable entity than other MBC presentations. However, only few retrospective series and data from selected randomized controlled trials have been reported so far. Methods: Using the French national multicenter ESME (Epidemiological Strategy and Medico Economics) Data Platform, the primary objective of our study was to compare the overall survival (OS) of patients with BO versus non-BO MBC at diagnosis, with adjustment on main prognostic factors using a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1), describe treatment patterns, and estimate factors associated with OS. Results: Out of 20,095 eligible women, 5041 (22.4%) patients had BO disease [hormone-receptor positive (HR+)/human epidermal growth-factor-receptor-2 negative (HER2−), n = 4 102/13,229 (31%); HER2+, n = 644/3909 (16.5%); HR−/HER2−, n = 295/2 957 (10%)]. BO MBC patients had a better adjusted OS compared with non-BO MBC [52.1 months (95% confidence interval (CI) 50.3–54.1) versus 34.7 months (95% CI 34.0–35.6) respectively]. The 5-year OS rate of BO MBC patients was 43.4% (95% CI 41.7–45.2). They also had a better PFS1 [13.1 months (95% CI 12.6–13.8) versus 8.5 months (95% CI 8.3–8.7), respectively]. This observation could be repeated in all subtypes. BO disease was an independent prognostic factor of OS [hazard ratio 0.68 (95% CI 0.65–0.72), p < 0.0001]. Results were concordant in all analyses. Conclusion: BO MBC patients have better outcomes compared with non-BO MBC, consistently, through all MBC subtypes.

Objective Response to Chemotherapy As a Potential Surrogate End Point of Survival in Metastatic Breast Cancer Patients

2005 ◽  
Vol 23 (22) ◽  
pp. 5117-5125 ◽  
Author(s):  
Paolo Bruzzi ◽  
Lucia Del Mastro ◽  
Maria P. Sormani ◽  
Lars Bastholt ◽  
Marco Danova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Response ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Experimental Treatment ◽  
Breast Cancer Patients ◽  
End Point ◽  
Response To Chemotherapy

Purpose To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer. Patients and Methods We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy. Results The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months). Conclusion These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.

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