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Pertuzumab as second‑ or later‑line therapy for human epidermal growth factor receptor 2‑positive metastatic breast cancer: A clinical experience.

ABSTRACT: Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. The present study assessed the therapeutic regimens, toxicities and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive pertuzumab as a first-line therapy. Physicians from nine major Swiss oncology centers retrospectively completed a questionnaire for each pertuzumab-naive patient who was treated with pertuzumab as a second- or later-line therapy. Of 35 patients with HER2-positive mBC (median age, 49 years; range, 35-87 years), 14 received pertuzumab as a second-line therapy, 6 as a third-line therapy, and 15 as a fourth- or later-line therapy. A total of 20 patients (57%) died during the study period. The median overall survival was 74.2 months (95% confidence interval, 47.6-139.8 months). Grade (G) 3/4 adverse events (AEs) were reported in 14% of patients, with only 1 patient discontinuing therapy due to pertuzumab-related toxicities. The most common AE was fatigue (overall, 46%; G3, 11%). Overall, congestive heart disease occurred in 14% of patients (G3, 6%), nausea in 14% of patients (all G1), and myelosuppression in 12% of patients (G3, 6%). In conclusion, the median overall survival of patients who underwent second- or later-line pertuzumab treatment was similar to that reported for patients who underwent first-line pertuzumab treatment, and the safety profile was acceptable. These data support the use of pertuzumab for second- or later-line therapy when it was not administered as first-line therapy.

SUBMITTER: Biskup E

PROVIDER: S-EPMC10251341 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Pertuzumab as second‑ or later‑line therapy for human epidermal growth factor receptor 2‑positive metastatic breast cancer: A clinical experience.

Biskup Ewelina E Sartorius Céline Montavon CM Müller Andreas A Leo Cornelia C Nussbaum Catrina Uhlmann CU Georgescu Margarint Elena Laura EL Koychev Daniel D Schreiber Alexander A Taverna Christian C Thorn David D Vetter Marcus M

Molecular and clinical oncology 20230518 1

Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 (<i>HER2</i>)-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. The present study assessed the therapeutic regimens, toxicities and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive ...[more]

PMID: 37303973

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Project description:BackgroundWe analyzed real-world practice of second-line treatment in hormone receptor (HR)+ human epidermal growth factor receptor-2 (HER2)- metastatic breast cancer (MBC) following the first-line CDK4/6 inhibitor with letrozole. In addition, we evaluated the relationship between second-line treatment strategies and survival outcome.MethodsUsing the clinical data warehouse, clinical information including MBC diagnosis, treatment and survival outcomes were collected.ResultsIn total, 305 patients were treated with the first-line palbociclib plus letrozole, and we evaluated 166 patients who were treated with second-line treatment. Of the 166 patients, 28.5% were treated with capecitabine (C), followed by exemestane with everolimus (EE) (27.3%) or cytotoxic chemotherapy other than capecitabine (T) (18.8%) and fulvestrant-based treatment or endocrine monotherapy (F) (12.7%). Eighteen patients (10.9%) were enrolled in clinical trials (CT). With regard to treatment strategies, and the median progression-free survival of second-line treatment in a metastatic setting (PFS2) was 7.4 months with C, 5.2 months with EE, 4.8 months with T, 3.6 months with F, and 3.6 months with CT (p = 0.066). In patients with visceral organ disease progression, C (31.3%) or T(31.3%) was the most common second-line treatment followed by EE (21.9%). Most of the 47 patients with bone metastasis alone were treated with EE (38.2%), followed by C (23.4%) and F (21.3%) (p = 0.008). The median overall survival of second-line treatment in a metastatic setting (OS2) was 42.3 months with C, 35.7 months with F, 30.7 months with EE, and 23.1 months with T. The median OS2 for those in CT was not reached (p = 0.064). ER driven BC, disease progression site and PFS2 were associated with OS and OS2 in HR+HER2- MBC (ps < 0.05).ConclusionsWe suggested the second line treatment strategy was important to improve prognosis in patients with HR+/HER2- MBC, especially given the recent standardization of first-line treatment and the many available second-line options.

Project description:Importance:Taxanes with trastuzumab and pertuzumab for initial treatment of human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-positive metastatic breast cancer is associated with improved progression-free survival (PFS) and overall survival. While continued use of trastuzumab in therapeutic combinations after disease progression is standard, the efficacy of continuing pertuzumab is unknown. Objective:To evaluate the efficacy and safety of pertuzumab in combination with gemcitabine and trastuzumab after prior treatment with pertuzumab for ERBB2-positive metastatic breast cancer. Design, Setting, and Participants:This is a phase 2 single-arm clinical trial of dual anti-ERBB2 therapy after prior treatment with pertuzumab. The study took place at a single academic center from March 2015 to April 2017 among women with ERBB2-positive metastatic breast cancer, prior pertuzumab-based treatment, and 3 or fewer prior chemotherapy regimens. Data were analyzed between January 2019 and March 2019. Intervention:Treatment consisted of gemcitabine, 1200 mg/m2 (later amended to 1000 mg/m2) on days 1 and 8 every 3 weeks, plus trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) once every 3 weeks. Main Outcomes and Measures:The primary end point was 3-month PFS. Based on prior trials, a target rate of 70% or higher was selected as the promising progression-free rate at 3 months. Secondary outcomes included safety, tolerability, and overall survival. Results:A total of 45 patients (median [range] age, 57.1 [31.7-77.2] years) were enrolled; 22 (49%) were treated in the second-line setting, and 23 (51%) were treated in the third-line setting or beyond. Of these, 22 (49%) received prior trastuzumab emtansine (T-DM1). At a median (range) follow-up of 27.6 (8.3-36.0) months, 3-month PFS was 73.3% (95% CI, 61.5%-87.5%). Overall, median PFS was 5.5 months (95% CI, 5.4-8.2 months). Treatment was well tolerated, with no occurrences of febrile neutropenia or symptomatic left ventricular systolic dysfunction. Conclusions and Relevance:In this phase 2 trial, treatment with gemcitabine, trastuzumab, and pertuzumab after prior pertuzumab-based therapy for ERBB2-positive metastatic breast cancer was associated with a 3-month PFS rate of 73.3% and was well tolerated. Continuation of pertuzumab beyond progression was associated with apparent clinical benefit. Trial Registration:ClinicalTrials.gov identifier: NCT02252887.

Project description:AimThis study aimed to compare anti-epidermal growth factor receptor (anti-EGFR) therapy and anti-vascular endothelial growth factor therapy as first-line and second-line therapies in patients with KRAS exon 2 codon 12/13 wild-type (KRAS-WT) metastatic colorectal cancer (mCRC).MethodsMajor databases were systematically searched. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (95% CIs) were used to estimate the effect measures. Review Manager software version 5.3 was used for statistical analysis.ResultsSeven trials including ten articles were eligible in the meta-analysis. The patients treated with anti-EGFR as first-line therapy showed a longer overall survival (OS) for KRAS-WT and all RAS wild-type (RAS-WT) mCRC (HR =0.81, 95% CI: 0.72-0.92, P<0.01, n=5; HR =0.78, 95% CI: 0.66-0.93, P<0.01, n=3, respectively). The objective response rate (ORR) was better with the anti-EGFR therapy for KRAS-WT and all RAS-WT mCRC (OR =1.32, 95% CI: 1.11-1.56, P<0.01, n=5; OR =1.55, 95% CI: 1.21-2.00, P<0.01, n=3, respectively). There was no difference in progression-free survival (PFS) for KRAS-WT mCRC and all RAS-WT mCRC between the two groups (HR =1.00; 95% CI: 0.92-1.09, P=0.99, n=4; HR =0.92, 95% CI: 0.71-1.19, P=0.52, n=3, respectively). In addition, two trials provided data on the second-line therapy; there was no significant difference in OS and PFS for the second-line therapy, but a significant improvement in ORR was found in the anti-EGFR group (OR =1.91, 95% CI: 1.16-3.16, P=0.01, n=2). No difference in the conversion therapy (OR =1.34; 95% CI: 0.91-1.99; P=0.14, n=4) was observed between the two therapies.ConclusionOur results indicate that anti-EGFR therapy is superior to anti-vascular endothelial growth factor therapy for OS and ORR as a first-line therapy for KRAS-WT mCRC. In the second-line therapy, there was no significant difference in the survival outcomes on the basis of OS and PFS between the two groups. However, ORR improved significantly in the anti-EGFR group.

Project description:The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2 years in 2001 (prior introduction of trastuzumab) to more than 4 years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice. The current consensus includes horizontal dual blockade (trastuzumab + pertuzumab) with taxanes or vinorelbine in the first line, followed by trastuzumab-emtansine (T-DM1) in the second line, with addition of lapatinib in the later lines of treatment. However, the fast and simultaneous development of new drugs led to a relative shortage of clinical evidence to support this sequence. Triple-positive breast cancers (TPBC), which express both hormonal receptors and HER2, constitute nearly half of HER2-positive cases. For these tumors, the current consensus is to add endocrine therapy after completion of cytotoxic treatment. Again, this consensus is not fully evidence-based. In view of the recent progress in treatment of estrogen-receptor positive breast cancers, a series of trials is evaluating addition of CDK4/6 inhibitors, aromatase inhibitors or fulvestrant to HER2-targeted and cytotoxic chemotherapy in TPBC patients. Despite the remarkable progress in treatment of HER2-positive breast cancer, metastatic disease is still incurable in the majority of patients. A wide range of novel therapies are under development to prevent and overcome resistance to current HER2-targeted agents. This review discusses pivotal clinical trials that have shaped current clinical practices, the current consensus recommendations, and the new experimental treatments in metastatic HER2-positive breast cancer.

Dataset Information

Pertuzumab as second‑ or later‑line therapy for human epidermal growth factor receptor 2‑positive metastatic breast cancer: A clinical experience.

Publications

Pertuzumab as second‑ or later‑line therapy for human epidermal growth factor receptor 2‑positive metastatic breast cancer: A clinical experience.

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