Novel HER2 Inhibitor Offers Manageable Toxicity, Anti-Tumor Activity in Metastatic Breast Cancer

Excerpt:

“A phase I trial found that the HER2 inhibitor ONT-380 had a lower incidence of certain adverse events associated with this class of agent and notable anti-tumor activity in heavily pretreated patients with HER2-positive metastatic breast cancer (MBC).

” ‘Though existing targeted therapies are improving outcomes in patients with HER2-positive MBC, disease resistance does eventually develop in most patients,’ wrote study authors led by Stacy Moulder, MD, of the MD Anderson Cancer Center in Houston. Also, some agents preclude combination with other regimens due to off-target effects such as skin rash and diarrhea.”

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Novel Antibody-Drug Conjugate Targets Triple-Negative Breast Cancer

Excerpt:

“The antibody-drug conjugate sacituzumab govitecan (IMMU-132) produced high objective response rates, many of them quite durable, in a multicenter study of heavily pretreated patients with metastatic triple-negative breast cancer, presented at the 2016 San Antonio Breast Cancer Symposium.

“Trop-2 is a calcium signal transducer that drives tumor growth and has shown promise as a novel therapeutic target in triple-negative breast cancer, since the majority of these tumors express Trop-2. Sacituzumab govitecan targets Trop-2 and selectively delivers high doses of SN-38, the active metabolite of irinotecan that is 1,000 times more active than the parent compound. In addition to drug delivery, sacituzumab govitecan potentially also activates antibody-dependent cell-mediated cytotoxicity.”

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Dual HER2-Blockade Plus AI Shows Promise in HER2+/ER+ Breast Cancer

Excerpt:

“Data from the phase II PERTAIN trial presented late last year at the 2016 San Antonio Breast Cancer Symposium (SABCS) showed that adding an aromatase inhibitor (AI) to pertuzumab (Perjeta) and trastuzumab (Herceptin) extended progression-free survival (PFS) by over 3 months versus trastuzumab plus an AI in patients with HER2-positive, HR-positive locally advanced or metastatic breast cancer.

“The median PFS was 18.89 months with the pertuzumab triplet compared with 15.80 months for trastuzumab and an AI alone (HR, 0.65; 95% CI, 0.48-0.89; P = .007). The objective response rates were 63.3% versus 55.7%, respectively.”

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Fulvestrant Prolongs PFS for Women with Hormone Receptor– Positive Advanced Breast Cancer

Excerpt:

“Fulvestrant prolonged PFS compared with anastrozole among women with hormone receptor– positive locally advanced or metastatic breast cancer who have not received previous endocrine therapy, according to a phase 3, randomized, double blind trial published in The Lancet.

” ‘The primary endpoint of this phase 3 study was met, with patients receiving fulvestrant having a significantly longer PFS than patients receiving anastrozole,’ John F.R. Robertson, MD, a professor at University of Nottingham Medical School and Royal Derby Hospital Centre in Derby, United Kingdom, and colleagues wrote. ‘This represents a meaningful and relevant finding for which clinical data are limited.’ ”

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Pegram Sheds Light on Margetuximab in HER2+ Breast Cancer

Excerpt:

“The Fc-modified monoclonal antibody margetuximab in combination with chemotherapy may offer a new treatment option for patients with HER2-positive metastatic breast cancer.

“In the ongoing phase III SOPHIA trial (NCT02492711), researchers are comparing margetuximab plus chemotherapy with trastuzumab (Herceptin) plus chemotherapy. In a previous phase I study, margetuximab demonstrated single-agent activity in HER2-positive tumors, leading researchers to explore the regimen in the phase III trial.”

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In Metastatic Breast Cancer Treatment, Not All CDK Inhibitors Are Equal


Doctors prescribe drugs known as CDK inhibitors to treat some women with estrogen-receptor-positive (ER+) metastatic breast cancer. Research into these drugs is ongoing, and new, promising CDK inhibitor options are on the horizon. Here, I address the current outlook for CDK inhibitors in ER+ breast cancer.

First, some background: ER+ breast cancers comprise about 70% of all breast cancers. The name reflects the fact that cells of these cancers express estrogen receptors (ERs), which are protein features targeted by many treatment strategies for this cancer type. The estrogen receptor (ER) protein is a treatment target not only because “it is there,” but mainly because it drives tumor cell proliferation in ER+ breast cancer. The activity of the ER depends on its binding to the hormone estrogen, and treatments known as endocrine drugs aim to prevent this interaction. Some endocrine drugs inhibit the synthesis of estrogen in the body (e.g., aromatase inhibitors, such as letrozole and anastrozole), and others prevent the interaction of estrogen with ERs (e.g., ER modulators such as tamoxifen, or the pure anti-estrogen drug fulvestrant). The problem of course is that, in metastatic breast cancer, resistance develops to each and every endocrine drug used. Continue reading…


Brain Mets Can Acquire HER2-Positivity in HER2-Negative Breast Cancer Patients

Excerpt:

“Brain metastases from primary breast cancer tumors often acquire clinically actionable genetic alterations, according to a small study. About one fifth of ERBB2/HER2-negative cases switched to HER2-positivity in the brain metastases.

” ‘Limited therapeutic options exist for patients with brain metastases,’ wrote study authors led by Nolan Priedigkeit, BS, of the University of Pittsburgh. ‘ERBB2/HER2-positive brain metastases have demonstrated encouraging responses to ERBB2/HER2-targeted therapies in recent clinical trials.’ ERBB2/HER2-negative brain metastases, however, have shown no such response.”

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Anti-CDK4/6 Boosts PFS in Metastatic Breast Cancer

Excerpt:

“The addition of a targeted agent to endocrine therapy for metastatic breast cancer led to unprecedented improvement in progression-free survival (PFS) that will have a ‘paradigm changing’ effect on clinical management, an investigator said here.

“Patients who received the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib in addition to letrozole (Femara) had a 44% reduction in the PFS hazard compared with patients treated with letrozole alone. The median PFS (primary endpoint) was 14.7 months with letrozole but had yet to be reached with letrozole plus ribociclib, ‘but it is expected to far exceed what the control arm did,’ Gabriel N. Hortobagyi, MD, reported at the European Society for Medical Oncology (ESMO) conference.”

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Sacituzumab Govitecan Elicits Durable Responses for Pretreated TNBC

Excerpt:

“Treatment with sacituzumab govitecan (IMMU-132) was well-tolerated and induced durable responses, some lasting longer than 1 year, for heavily pretreated patients with metastatic triple-negative breast cancer (TNBC), according to findings from an ongoing phase I/II study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).

“In the single-arm trial, the confirmed objective response rate (ORR) was 30% with sacituzumab govitecan, and the duration of response was 8.9 months (95% CI, 6.1-11.3). The median progression-free survival was 6.0 months (95% CI, 5.0-7.3) and the median overall survival was 16.6 months (95% CI, 11.1-20.6).”

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