Earlier Indicator of Palbociclib Response Found for Patients with Breast Cancer

Excerpt:

“According to findings published in Nature Communications, a blood test detecting early changes in circulating tumor DNA (ctDNA) may provide earlier indication of whether patients with hormone receptor–positive, HER2-negative breast cancer are responding to the CDK4/6 inhibitor palbociclib (Ibrance).

“The test could detect a response within 2 to 3 seeks, said investigators with The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. Women currently wait 2 to 3 months to find out if palbociclib treatment is working for them.”

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Updated Data from Phase 3 Trial of Ibrance® (Palbociclib) plus Letrozole in ER+, HER2- Metastatic Breast Cancer Confirm Improvement in Progression-Free Survival

Excerpt:

“Pfizer Inc. (NYSE:PFE) today announced updated progression-free survival (PFS) results from the Phase 3 PALOMA-2 trial reinforcing the clinical benefit of IBRANCE® (palbociclib) combined with letrozole. The data, which will be presented at the 2017 San Antonio Breast Cancer Symposium (SABCS) on December 8 [abstract #P5-21-03], demonstrate that the combination of IBRANCE plus letrozole reduced the risk of disease progression by 44 percent and improved median PFS by more than one year compared to letrozole plus placebo (27.6 months [95% CI: 22.4, 30.3] vs 14.5 months [95% CI: 12.3, 17.1]) when used as the initial treatment for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) metastatic breast cancer (HR=0.56 [95% CI: 0.46, 0.69]). This updated, post-hoc analysis included a median follow-up of more than three years, which is the longest to date of any Phase 3 study of a CDK 4/6 inhibitor.”

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EU, US Approvals for Faslodex Combinations

Excerpt:

“AstraZeneca’s Faslodex has been cleared on both sides of the Atlantic for use in combination with a CDK4/6 inhibitor.

“In the EU, the drug’s use has been approved for use alongside the CDK4/6 inhibitor palbociclib to treat a certain form of breast cancer, in the US it can be prescribed in combination with the CDK4/6 inhibitor abemaciclib.

“Both the European Commission and US Food and Drug Administration have approved the combination for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.”

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Fulvestrant Gains New Breast Cancer Indication

Excerpt:

“The FDA expanded the indications for fulvestrant (Faslodex) to include use as first-line monotherapy in postmenopausal women with estrogen receptor-positive, HER-2 negative breast cancer, drugmaker AstraZeneca said Monday.

“Previously the drug was approved as second-line monotherapy for women failing anti-estrogen therapy, and as second-line combination therapy with palbociclib (Ibrance). It was first approved by the FDA in 2002.”

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Potential Treatment for Brain Cancer as Drug Shrinks Tumours

Excerpt:

“An international team of researchers has found a drug previously approved to treat breast cancer could also be used to shrink medulloblastoma, a common form of childhood brain tumour.

“The discovery, made by The University of Queensland’s Institute for Molecular Bioscience and the Fred Hutchinson Cancer Research Center in Seattle, has led to a clinical trial using the drug palbociclib to treat children with medulloblastoma, the most common malignant brain tumour found in children.”

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Expert Explains Individualized Decision on Endocrine Therapy Beyond 5 Years in Breast Cancer

Excerpt:

“Endocrine therapy remains an integral part of the treatment paradigm for patients with estrogen receptor (ER)–positive breast cancer; however, questions remain on which patients should continue their therapy beyond 5 years.

” ‘The idea [is] that most patients with hormone receptor (HR)-positive breast cancer who are still on endocrine therapy at 5 years are going to merit some sort of discussion about whether they should continue or not, and it is okay to individualize that decision on the basis of the patient preferences, side effects, and symptom burden,’ said Amye J. Tevaarwerk, MD.”

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The Trouble With KRAS


Mutations in the gene that encodes the KRAS protein are frequently encountered in various human cancers. They are found in about 30% of non-small cell lung cancers (NSCLCs), making KRAS the single most common gene mutated in this cancer. The rate of KRAS mutations in other cancers, such as pancreatic or colorectal, is even higher.

A mutant KRAS protein that is always in the “on” position activates many signaling pathways, many of which lead to unrestrained growth and proliferation of cancer cells. This makes KRAS an appealing treatment target. However, challenges abound, and researchers are exploring several different approaches to treating KRAS-mutant cancers.

Unlike mutations in proteins known as receptor tyrosine kinases, like EGFR or ALK, mutated KRAS is a very difficult protein to target with cancer drugs. (So much so that the National Institutes of Health (NIH) has undertaken a special effort to intensify the effort towards successful targeting of mutant KRAS, known as the RAS Initiative.) Continue reading…


Drug Combination Shows Benefit in RAS-Driven Cancers

Excerpt:

“Cancers driven by the RAS oncogene are aggressive and difficult to treat, and thus far precision drugs haven’t been able to target the mutant RAS gene successfully.

“But in a presentation at the American Association for Cancer Research Annual Meeting on Monday, April 3, 2017 at 10:30 a.m., in Washington DC, Dana-Farber Cancer Institute scientists said a number of in a small study with RAS-driven lung, ovarian, and thyroid cancers got long-term clinical benefit from a combination of two drugs that targeted molecular pathways controlled by the RAS gene.

” ‘Between one-quarter and one-third of patients got long-term clinical benefit,’ said Geoffrey Shapiro, MD, PhD, director of Dana-Farber’s Early Drug Development Center. ‘Several patients were on the drugs for more than a year, and one patient has been on treatment for two and a half years. And these were heavily-treated patients without many options.’ ”

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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…