Combination of radiotherapy and double blockade HER2 with pertuzumab and trastuzumab for HER2-positive metastatic or locally recurrent unresectable and/or metastatic breast cancer: Assessment of early toxicity

Ajgal, Zahra; Percin, Sixtine De; Dièras, Véronique; Pierga, Jean‐Yves; Campana, F.; Fourquet, A.; Kirova, Youlia

doi:10.1016/j.canrad.2016.10.002

Cited by 23 publications

(22 citation statements)

References 28 publications

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“…Studies reported at least 99% enrollment of female patients, except for one study that reported enrolling 77% and 82% female patients in two study cohorts [16]. Age (median) at enrollment ranged from 47 to 57 years [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. In 12 studies, 54% to 100% of patients were white [15-17, 19-21, 23-26, 29, 31].…”

Section: Resultsmentioning

confidence: 99%

“…Most studies (n = 11) were conducted in an international setting, enrolling patients in multiple countries and continents. Three studies were conducted solely in the United States (US) [17,24,31], while others enrolled patients in both the US and Japan [27], Europe [16], France [18], or China [30].…”

Section: Resultsmentioning

confidence: 99%

“…Missing information on previous treatment lines in the metastatic setting e Treatment-related ILD events were confirmed by an independent adjudication committee f Deaths were attributed to ILD by independent adjudication and were initially reported as respiratory failure (n = 1), acute respiratory failure (n = 1), lymphangitis (n = 1), or pneumonitis (n = 1) trastuzumab studies reported at least one case of specifically ILD [19,22]. Seven trastuzumab studies reported at least one case of pneumonitis [17-19, 22-24, 28], of which six studies reported at least one case of grade 3 or higher pneumonitis and one study reported grade 1-2 pneumonitis cases related to radiotherapy [18]. Four studies assessed patients who received trastuzumab combined with an mTOR inhibitor, including everolimus [19,22,23] and sirolimus [17].…”

Section: Trastuzumabmentioning

confidence: 99%

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Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer

Hackshaw

Danysh

Singh

et al. 2020

Breast Cancer Res Treat

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Purpose Anti-human epidermal growth factor receptor 2 (HER2) therapies are associated with interstitial lung disease (ILD), also referred to as pneumonitis. In this literature review, we describe the incidence of ILD among patients with HER2-positive metastatic breast cancer (MBC) receiving anti-HER2 therapies, and we describe existing recommendations for monitoring and managing drug-induced ILD among these patients. Methods We searched PubMed and Embase to identify clinical trials and postmarket observational studies that investigated anti-HER2 therapies for HER2-positive MBC, reported on ILD, and were published during January 1, 2009 to July 15, 2019. Articles were screened by two researchers; data were extracted from the full-text articles. Results The 18 articles selected for this review assessed 9,886 patients who received trastuzumab (8 articles), lapatinib (4 articles), trastuzumab emtansine (3 articles), trastuzumab deruxtecan (2 articles), or trastuzumab duocarmazine (1 article). The overall incidence of all-grade ILD was 2.4% (n = 234), with 66.7% (n = 156) occurring as grade 1-2 events, 0.5% grade 3-4 (n = 54; incidence), and 0.2% grade 5 (n = 16; incidence). The highest ILD incidence (21.4%) was among patients receiving trastuzumab combined with everolimus and paclitaxel. Ten studies indicated that ILD events were managed via dose interruption, dose reduction, or treatment discontinuation; two studies included detailed guidelines on managing druginduced ILD. Conclusions ILD is a well-described adverse drug reaction associated with several anti-HER2 drugs. Published ILD management guidelines are available for few anti-HER2 treatment regimens; however, guidance for monitoring for anti-HER2 drug-induced ILD is lacking.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Trastuzumabmentioning

confidence: 99%

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Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer

Hackshaw

Danysh

Singh

et al. 2020

Breast Cancer Res Treat

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“…However, these data have to be validated by investigating larger cohorts of analogously treated patients. Therefore, also the poorly investigated potential enhancers of posttherapeutic lung tissue complications in sequential chemoradiation pertuzumab [ 55 ], and the meanwhile phased-out vaccine tecemotide [ 56 ], did not deliver valid information about their real riskiness in more complex sequential regimens.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, pertuzumab [ 55 ] and the meanwhile phased-out vaccine tecemotide [ 56 , 57 ] were candidates for scarcely investigated potential enhancers of posttherapeutic lung tissue complications in sequential chemoradiation. A small cohort of patients received premedication based on statins to treat hypercholesterolemia, potentially acting as pneumonitis protectors.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of pneumonitis following radiotherapy of breast cancer – A prospective study

et al. 2018

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Aimof this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma.Patients and methodsA total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment.ResultsA pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis.ConclusionsThe rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

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Trapping all ERBB ligands decreases pancreatic lesions in a murine model of pancreatic ductal adenocarcinoma

Hedegger¹,

Blutke²,

Hommel

et al. 2023

Molecular Oncology

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Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of cancers. Attempts to develop targeted therapies still need to be established. Some oncogenic mechanisms in PDAC carcinogenesis harness the EGFR/ERBB receptor family. To explore the effects on pancreatic lesions, we attempted simultaneous blockade of all ERBB ligands in a PDAC mouse model. To this end, we engineered a molecular decoy, TRAP‐FC, comprising the ligand‐binding domains of both EGFR and ERBB4 and able to trap all ERBB ligands. Next, we generated a transgenic mouse model (CBATRAP/0) expressing TRAP‐FC ubiquitously under the control of the chicken‐beta‐actin promoter and crossed these mice with KRASG12D/+ mice (Kras) to generate Trap/Kras mice. The resulting mice displayed decreased emergence of spontaneous pancreatic lesion areas and exhibited reduced RAS activity and decreased activities of ERBBs, with the exception of ERBB4, which showed increased activity. To identify the involved receptor(s), we employed CRISPR/Cas9 DNA editing to singly delete each ERBB receptor in the human pancreatic carcinoma cell line Panc‐1. Ablation of each ERBB family member, especially the loss of EGFR or ERBB2/HER2, altered signaling downstream of the other three ERBB receptors and decreased cell proliferation, migration, and tumor growth. We conclude that simultaneously blocking the entire ERBB receptor family is therapeutically more effective than individually inhibiting only one receptor or ligand in terms of reducing pancreatic tumor burden. In summary, trapping all ERBB ligands can reduce pancreatic lesion area and RAS activity in a murine model of pancreatic adenocarcinoma; hence, it might represent a promising approach to treat PDAC in patients.

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Combination of radiotherapy and double blockade HER2 with pertuzumab and trastuzumab for HER2-positive metastatic or locally recurrent unresectable and/or metastatic breast cancer: Assessment of early toxicity

Cited by 23 publications

References 28 publications

Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer

Incidence of pneumonitis/interstitial lung disease induced by HER2-targeting therapy for HER2-positive metastatic breast cancer

Occurrence of pneumonitis following radiotherapy of breast cancer – A prospective study

Trapping all ERBB ligands decreases pancreatic lesions in a murine model of pancreatic ductal adenocarcinoma

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