Planned interim analysis of PATRICIA: An open-label, single-arm, phase II study of pertuzumab (P) with high-dose trastuzumab (H) for the treatment of central nervous system (CNS) progression post radiotherapy (RT) in patients (pts) with HER2-positive metastatic breast cancer (MBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2074-2074 ◽  
Author(s):  
Nancy U. Lin ◽  
Alisha Stein ◽  
Alan Nicholas ◽  
Anita M. Fung ◽  
Priya Kumthekar ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Objective Response ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Her2 Positive ◽  
Open Label ◽  
Ventricular Ejection Fraction ◽  
Safety Signals

2074 Background: There is currently no clear standard of care to address the management of recurring/multiple intracranial metastases post RT in HER2-positive MBC. The ongoing PATRICIA study (NCT02536339) is evaluating the safety and efficacy of P in combination with high-dose h for patients with HER2-positive MBC with CNS metastases who have CNS progression following RT. Reported herein are results from the protocol-specified interim analysis of PATRICIA. Methods: All eligible patients must have measurable (≥10 mm) CNS progression post RT, and stable non-CNS disease. Patients receive P (840-mg loading dose, then 420 mg every 3 weeks) and high-dose h (6 mg/kg weekly). The primary efficacy endpoint is objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. The interim analysis was planned after 15 patients were enrolled and had ≥2 left ventricular ejection fraction (LVEF) measurements, 2 cycles of study drugs, and 2 response measurements. The study would proceed to full enrollment (n=40) if objective response or stable disease in the CNS was observed in ≥1 of 15 patients and <2 of 15 patients develop congestive heart failure (CHF) related to P or H. Results: As of Sept 6, 2016, 15 patients had been enrolled across 9 sites. Median treatment duration was 4.4 (range 1.2−8.3) months. Six patients discontinued treatment (5 for disease progression; 1 for symptomatic deterioration). Range for duration of response was 1.4−3.3 months. There were no new safety signals for P combined with high-dose h treatment. No patients had CHF or a clinically significant drop in LVEF. Conclusions: Based on early evidence of clinical benefit (ORR 20%) and a lack of new safety signals, the safety and futility boundaries for PATRICIA have been passed and study enrollment continues. Clinical trial information: NCT02536339. [Table: see text]

A phase III, randomized, double-blind, placebo (Pla)-controlled study of pertuzumab (P) + trastuzumab (H) + docetaxel (D) versus Pla + H+ D in previously untreated HER2-positive locally recurrent/metastatic breast cancer (LR/MBC) (PUFFIN).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1026-1026 ◽  
Author(s):  
Binghe Xu ◽  
Wei Li ◽  
Qingyuan Zhang ◽  
Shao Zhimin ◽  
Wang Xiao Jia ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Her2 Positive ◽  
Double Blind ◽  
Ventricular Ejection Fraction

1026 Background: In CLEOPATRA (NCT00567190), adding P to H + D significantly improved progression-free and overall survival (PFS/OS) v Pla + H + D in patients (pts) with previously untreated HER2-positive LR/MBC. PUFFIN (NCT02896855) is a China bridging study; the objective being to assess consistency of efficacy with CLEOPATRA. Methods: Pts with previously untreated HER2-positive LR/MBC were randomized 1:1 to P + H + D or Pla + H + D, stratified by visceral v non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR in pts with measurable baseline disease), OS, and safety. The target sample size (240) was determined based on the consistency threshold for PFS, defined as hazard ratio (HR) < 0.81, which maintains ≥ 50% of the risk reduction determined in CLEOPATRA (HR 0.62). Results: Two hundred forty-three pts were randomized. Baseline/disease characteristics and prior therapies were generally balanced between arms. For PFS, the HR was 0.69 (95% CI 0.49, 0.99) in the ITT population. No cases of heart failure or symptomatic left ventricular ejection fraction decline were reported. Efficacy/safety are shown in the table. Conclusions: PUFFIN met its primary endpoint. Overall, efficacy data were consistent with CLEOPATRA (ITT population and Asian subgroup). Safety was also consistent and in line with the known P safety profile, with no new or unexpected signals reported. PUFFIN adds to the totality of data with P in previously untreated HER2-positive LR/MBC, and supports the favorable benefit–risk profile of P in Chinese pts. Clinical trial information: NCT02896855. [Table: see text]

scholarly journals Subcutaneous trastuzumab with pertuzumab and docetaxel in HER2-positive metastatic breast cancer: Final analysis of MetaPHER, a phase IIIb single-arm safety study

2021 ◽  
Author(s):  
Sherko Kuemmel ◽  
Carlo A. Tondini ◽  
Jacinta Abraham ◽  
Zbigniew Nowecki ◽  
Bartosz Itrych ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Subcutaneous Administration ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Abstract Purpose Intravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC. Methods In this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy. Results At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%. Conclusions Safety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies. Trial registration NCT02402712

Subcutaneous Trastuzumab with Pertuzumab and Docetaxel in HER2-Positive Metastatic Breast Cancer: Final Analysis of MetaPHER, A Phase 3b Single-Arm Safety Study

2020 ◽  
Author(s):  
Sherko Kümmel ◽  
Carlo Alberto Tondini ◽  
Jacinta Abraham ◽  
Zbigniew Nowecki ◽  
Bartosz Itrych ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Abstract BACKGROUND Intravenous trastuzumab, pertuzumab, and docetaxel is first-line standard of care for patients with HER2-positive metastatic breast cancer. Subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy has shown similar safety and tolerability to intravenous trastuzumab in patients with HER2-positive early and metastatic breast cancer; however, in the metastatic setting, this has yet to be shown globally.METHODS In this open-label, single-arm, multicenter phase 3b study, eligible patients were ≥18 years old with histologically/cytologically confirmed previously untreated HER2-positive metastatic breast cancer. All patients received ≥1 dose of subcutaneous trastuzumab (fixed-dose 600 mg) plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance dose: 420 mg/kg) and docetaxel (≥6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.RESULTS At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia. The most common grade ≥3 adverse events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.CONCLUSIONS Efficacy/safety results of subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in metastatic breast cancer are consistent with historical evidence of intravenous trastuzumab. These findings further support the body of evidence indicating that subcutaneous administration does not affect the safety and efficacy profile of trastuzumab in HER2-positive breast cancer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02402712 (date of registration: 30th March 2015)

Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1004-1004 ◽  
Author(s):  
J. Baselga ◽  
D. Cameron ◽  
D. Miles ◽  
S. Verma ◽  
M. Climent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Loading Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

1004 Background: T and P bind to different epitopes on the extra cellular domain of HER2. Unlike T, P binds to the dimerization domain and blocks homo- and hetero-dimerization of HER2 with other HER kinase family members. Xenograft models support the hypothesis that the complementary mechanisms of action could result in augmented efficacy when T and P are combined. Methods: Two-stage design, criteria to proceed to the 2nd stage were: ≥ 2 partial responses (PR) or 1 PR and 12 stable disease (SDs) or 13 SDs. Eligibility included: measurable, centrally-tested HER2 positive breast cancer; up to 3 lines of prior chemotherapy plus T (including adjuvant chemotherapy plus T); disease progression during T as most recent treatment for metastatic disease; baseline left ventricular ejection fraction (LVEF) ≥ 55% and no decrease of LVEF to below 50% during prior T treatment. Consenting Pts received T i.v. weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively (with re-loading dose if required) plus 420mg fixed dose of P i.v. every 3 weeks following loading dose 840mg. Study treatment was initiated within 9 weeks of the last dose of T given as most recent therapy. An independent data safety monitoring board has overseen the 1st stage safety data. Results: Recruitment into 1st stage is complete. The main adverse events were diarrhea (71%), fatigue (46%), nausea/vomiting (38%) and rash (25%). Most AE’s were mild to moderate (there was 1 case of Grade 3 diarrhea) and none was treatment-limiting. There were no clinical cardiac events, and central review revealed no case of fall in LVEF of ≥10% and to ≤50%. Response status: 5 confirmed PR (21%); 12 SD (50%). Responses have been observed in lymph node and liver metastases. Recruitment into the 2nd stage of the trial has commenced. Conclusions: The combination of the P and T is active and well tolerated in patients with pre-treated HER2 positive breast cancer which has progressed during treatment with T. No significant financial relationships to disclose.

A report of cardiac events in a phase II clinical study using trastuzumab combined with pertuzumab in HER2-positive metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1028-1028
Author(s):  
C. C. Portera ◽  
J. M. Walshe ◽  
N. Denduluri ◽  
A. W. Berman ◽  
U. Vatas ◽  
...  
Keyword(s):  
Chest Wall ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Erbb Receptors ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

1028 Background: T and P are humanized recombinant monoclonal antibodies (MoAB) that target different epitopes of HER2 extracellular domain. P blocks HER2’s ability to heterodimerize with other HER/ErbB receptors. Methods: This Ph II trial evaluates the efficacy and safety of T with P in patients (pts) with HER2+ (FISH +) MBC who had progressive disease (PD) on T-based therapy. Eligible pts must have had = 3 T-based regimens, normal (nl) left ventricular ejection fraction (EF=55%) and without significant cardiac history. Pts received IV T (6mg/kg) and P (420 mg) every 3 weeks (wks). EKG plus echocardiogram (ECHO) or cardiac MRI and tumor response were assessed every 3 and 6 wks, respectively. Results: Eleven pts received 39 (1 to 13) cycles, 1 pt achieved a partial response (PR) and 3 pts had stable disease. A total of 68 ECHOs and 8 cardiac MRIs were performed. Left ventricular systolic dysfunction (LVSD) with nl EKG was seen in 5 pts; Grade (Gr) 1 (n = 2) (EF 50–55%), Gr 2 (n = 2) (EF 40–50%) and Gr 3 (n = 1) (EF20–40%). Gr 2–3 events were associated with global hypokinesis. Gr 3 event was associated with symptomatic CHF. All 5 pts had received 240mg/m2 cumulative dose of doxorubicin, 2 pts (Gr 2–3) received chest wall radiation, and 1 pt (Gr 1) had HTN. Two pts with Gr 1–2 LVSD had a history of reduced EF during prior T-based treatment, which reversed to nl upon stopping T. Reduced EF appeared within 1–2 cycles, which returned to nl in 3 pts within 1wk to 3 months (mo) post discontinuing T/P. One pt had persistent Gr 2 LVSD 3 mo after the initial event. The pt with Gr 3 LVSD had extensive chest wall disease and died of PD and possibly CHF 2 mo after treatment termination. Conclusions: We observed Gr 1–3 LVSD in patients with HER2+ MBC who received dual MoAB treatment directed at HER2, in which very strict cardiac surveillance guidelines were required. One of 11 pts achieved PR and 1 pt had symptomatic CHF thus far. It is unknown whether the other events would have become symptomatic if treatment had continued. Further evaluation of the efficacy of combination T with P is required to define the overall risk and benefit. No significant financial relationships to disclose.

T-ACT (WJOG7112G): A randomized phase II study of weekly paclitaxel ± trastuzumab in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer refractory to trastuzumab combined with fluoropyrimidine and platinum.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS218-TPS218 ◽  
Author(s):  
Taito Esaki ◽  
Akitaka Makiyama ◽  
Tomomi Kashiwada ◽  
Ayumu Hosokawa ◽  
Junji Kawada ◽  
...  
Keyword(s):  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Rank Test ◽  
First Line ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Ventricular Ejection Fraction ◽  
Significance Level ◽  
Line Chemotherapy

TPS218 Background: Trastuzumab (Tmab) is a key drug for HER2 positive breast and gastric or gastro-esophageal junction (G/GEJ) cancer. While use of Tmab beyond progression (TBP) showed a benefit in HER2-positive metastatic breast cancer, clinical significance of TBP for HER2-positive G/GEJ cancer has not been clarified. Objective:This study compares the efficacy of paclitaxel (PTX) + Tmab with PTX alone in patients with unresectable or metastatic HER2-positive G/GEJ cancer who failed first-line chemotherapy with Tmab + fluoropyrimidine + platinum. Methods: Enrolled patients will be randomized to receive PTX (80 mg/m2, on day 1, 8 15, every 4 weeks) + Tmab (8 mg/kg loading dose and 6 mg/kg thereafter, on day 1, every 3 weeks) or PTX alone. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, time to treatment failure, response rate, disease control rate, safety, and translational biomarker research. A total of 69 events are required to achieve 80% power for one-sided log rank test with 10% significance level, expecting the median PFS of the PTX and the PTX + Tmab arms will be 3 and 5 months. In consideration of patient with censoring and dropout, the planned sample size is totally 90 patients. Major eligibility criteria are: HER2-positive advanced G/GEJ adenocarcinoma; refractory to first-line chemotherapy with fluoropyrimidine, platinum, and Tmab (at least three doses); within 6 weeks after last Tmab administration; no prior therapy with taxane or anti-HER2 drugs except Tmab; ECOG PS 0-2; adequate organ function; left ventricular ejection fraction ≥ 50%. Tumor tissue, blood serum, and circulating tumor DNA are collected before the study treatment for biomarker analyses to explore the predictive marker of the TBP strategy. As of September 2016, 89 patients were randomized. Clinical trial information: 000009297.

scholarly journals Dose-Dense Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/neu–Overexpressed/Amplified Breast Cancer Is Not Feasible Because of Excessive Diarrhea

2010 ◽  
Vol 28 (18) ◽  
pp. 2982-2988 ◽  
Author(s):  
Chau Dang ◽  
Nancy Lin ◽  
Beverly Moy ◽  
Steven Come ◽  
Steven Sugarman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
High Rate ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Grade 3 ◽  
Dose Dense

PurposeDose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel and trastuzumab (PT) is feasible. Lapatinib is effective in the treatment of human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer. We conducted a pilot study of dose-dense AC followed by PT plus lapatinib (PTL) followed by trastuzumab plus lapatinib (TL).Patients and MethodsPatients with stages I to III, HER2-positive breast cancer and left ventricular ejection fraction (LVEF) of ≥ 50% were enrolled. Treatment consisted of AC (60 mg/m2and 600 mg/m2) for 4 cycles every 2 weeks (with pegfilgrastim 6 mg on day 2) followed by paclitaxel (80 mg/m2) for 12 doses weekly plus trastuzumab and lapatinib. Trastuzumab (4 mg/kg loading dose, then 2 mg/kg weekly during paclitaxel then 6 mg/kg every 3 weeks after paclitaxel) and lapatinib (1,000 mg daily) were given for 1 year. The primary end points were feasibility defined as ≥ 80% patients completing the PTL phase without a dose delay/reduction and a cardiac event rate of ≤ 4%.ResultsFrom March 2007 to April 2008, we enrolled 95 patients. Median age was 46 years (range, 28 to 73 years). At a median follow-up of 22 months, 92 were evaluable. Of the 92 patients, 41 patients (45%) withdrew for PTL-specific toxicities. Overall, 40 (43%) of 92 patients had lapatinib dose reductions, and 27 (29%) of 92 patients had grade 3 diarrhea. Three patients (3%) had congestive heart failure; three patients dropped out because of significant asymptomatic LVEF decline during PTL followed by TL.ConclusionDose-dense AC followed by PTL and then followed by TL was not feasible because of a high rate of lapatinib dose reduction, mostly caused by unacceptable grade 3 diarrhea. Lapatinib (1,000 mg/d) was not feasible combined with weekly PT.

Phase Ib/II study of capecitabine 7/7 schedule with neratinib in patients with HER2-positive metastatic breast cancer (MBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15016-e15016
Author(s):  
Rui Wang ◽  
Jasmeet Chadha Singh ◽  
Serena Tsan-Lai Wong ◽  
Diana Lake ◽  
Neil M. Iyengar ◽  
...  
Keyword(s):  
Dose Level ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Irreversible Inhibitor ◽  
Ventricular Ejection Fraction ◽  
Phase Ib ◽  
Level 1

e15016 Background: Neratinib (N) is a potent irreversible inhibitor of HER1, HER2, and HER4. Capecitabine (X) at optimal dose of 7 days on and 7 days off schedule (7/7) is well-tolerated with low rates of ≥ grade (G3) diarrhea. Methods: We conducted phase Ib/II study of N with X (7/7) with loperamide and colestipol prophylaxis in patients (pts) with pretreated HER2+ MBC (NCT03377387). Eligible pts had normal left ventricular ejection fraction (≥ 50%), any and < 4 prior chemotherapy-based treatments in phase Ib and II, respectively. Primary endpoint of phase Ib is maximum tolerated dose (MTD) and phase II is response rate. Secondary endpoints are safety, tolerability, and progression-free survival. Exploratory endpoint is to quantify cell-free DNA (cfDNA), correlating with response. Phase Ib follows traditional 3+3 design with 4 dose levels. In phase II, if > 3/9 respond, study is expanded to 24. If > 10/24 respond, study is deemed successful. Results: As of 2-4-2021, 10 pts were enrolled in phase Ib. 4 pts were treated at dose level 1 (X at 1500 mg BID at 7/7 and N at 240 mg daily); 2/4 pts experienced with G3 diarrhea during cycle 1. Six pts were treated at dose level -1 (X at 1000 mg BID 7/7 and N at 240 mg daily); 1 (17%) developed G3 diarrhea. The MTD is X at 1000 mg BID 7/7 and N at 240 mg daily. Twenty-two of 24 pts have been enrolled in phase II. Of 22 pts, data show 6 with partial response, 8 with stable disease, 3 with progressive disease, and 5 have not been assessed radiographically. Overall, 6/22 (27.3%) and 1/22 (4.5%) had all G and G3 diarrhea, respectively. Other significant toxicities at MTD included G2 hand foot syndrome (n = 1, 4.5%), G1 fatigue (n = 1, 4.5%) and G1 nausea (n = 4, 18%). Conclusions: The MTD is X at 1000 mg BID at 7/7 and N at 240 mg daily. This combination is safe and well tolerated with G3 diarrhea rate of 4.5%, which is significantly lower than the X 14/7 schedule in NALA study. The phase II portion of the study is near completion and updated result will be presented. Analysis of cfDNA, to correlate with response for phase II portion, is ongoing. Clinical trial information: NCT03377387.

Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA4509-LBA4509 ◽  
Author(s):  
E. Van Cutsem ◽  
Y. Kang ◽  
H. Chung ◽  
L. Shen ◽  
A. Sawaki ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Data Monitoring Committee ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

LBA4509 Background: Advanced GC is an incurable disease; new and less toxic treatments are needed. HER2 overexpression has been reported in 6–35% of stomach and gastroesophageal tumors. Trastuzumab (H; Herceptin), a monoclonal antibody against HER2, has shown survival benefits when given with CT in patients (pts) with HER2-positive early and metastatic breast cancer. The ToGA study is the first randomized, prospective, multicenter, phase III trial to study the efficacy and safety of H in HER2- positive GC. Methods: Pts with HER2-positive gastroesophageal and gastric adenocarcinoma (locally advanced, recurrent, or metastatic) were randomized to receive H+CT (5-fluorouracil or capecitabine and cisplatin) q3w for 6 cycles or CT alone. H was given until disease progression. The primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival, time to progression, duration of response, and safety. An interim analysis was planned at 75% of deaths and the Independent Data Monitoring Committee recommended releasing the data as the pre-specified boundary was exceeded and median follow-up of pts was 17.1 months. Results: Tumors from 3,807 pts were centrally tested for HER2 status: 22.1% were HER2 positive (abstract #4556). 594 pts were randomized 1:1 at sites in Europe, Latin America, and Asia. Baseline characteristics were well balanced across arms. Median OS was significantly improved with H+CT compared to CT alone: 13.5 vs. 11.1 months, respectively (p=0.0048; HR 0.74; 95% CI 0.60, 0.91). ORR was 47.3% in the H+CT arm and 34.5% in the CT arm (p=0.0017). Safety profiles were similar with no unexpected adverse events in the H+CT arm. There was no difference in symptomatic congestive heart failure between arms. Asymptomatic left ventricular ejection fraction decreases were reported in 4.6% of pts in the H+CT arm and 1.1% in the CT arm. Conclusions: This first randomized trial investigating anti-HER2 therapy in advanced GC showed that H+CT is superior to CT alone. The OS benefit indicates that H is a new, effective, and well-tolerated treatment for HER2-positive GC. [Table: see text]

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