Z-Endoxifen Shows Promise as New Treatment for Common Breast Cancer Type

Excerpt:

“Z-endoxifen, a potent derivative of the drug tamoxifen, could itself be a new treatment for the most common form of breast cancer in women with metastatic disease. This finding was reported from a clinical trial conducted by researchers at Mayo Clinic and the National Cancer Institute, and published in the Journal of Clinical Oncology.

“The final results of a first-in-human phase I study of Z-endoxifen in women with estrogen receptor positive  showed that the treatment was safe and resulted in tumor shrinkage in women whose tumors had progressed on standard anti-estrogen therapies, including tamoxifen.”

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AKT Inhibitor Ipatasertib in Metastatic Triple-Negative Breast Cancer

Excerpt:

“The randomized phase II LOTUS trial has shown improved progression-free survival with the addition of the AKT inhibitor ipatasertib to paclitaxel in the first-line treatment of metastatic triple-negative breast cancer. These results were reported by Kim et al in The Lancet Oncology. The PI3K/AKT signaling pathway is frequently activated in triple-negative breast cancer.

“In the double-blind trial, 124 patients with unresectable locally advanced or metastatic disease from 44 sites in South Korea, the United States, France, Spain, Taiwan, Singapore, Italy, and Belgium were randomized between September 2014 and February 2016 to receive paclitaxel at 80 mg/m² on days 1, 8, and 15 with either ipatasertib at 400 mg (n = 62) or placebo (n = 62) once daily on days 1 to 21 every 28 days until disease progression or unacceptable toxicity. Stratification factors included tumor PTEN status as determined by immunohistochemistry; deficient expression of PTEN is associated with greater AKT pathway activation. The co-primary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low population.”

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Adjuvant Temozolomide in 1p/19q Non-Codeleted Anaplastic Glioma

Excerpt:

“Interim results of the phase III CATNON trial (EORTC study 26053-22054) indicate a survival benefit of adjuvant temozolomide in 1p/19q non-codeleted anaplastic glioma. These findings were reported in The Lancet by van den Bent et al.

“In the open-label 2 x 2 factorial trial, 745 adult patients with newly diagnosed disease were randomized 1:1:1:1 between December 2007 and September 2015 to receive radiotherapy (59.4 Gy in 33 fractions of 1.8 Gy) alone (n = 187) or with (n = 185) adjuvant temozolomide (12 4-week cycles of 150–200 mg/m² given on days 1–5) or to receive radiotherapy with concurrent temozolomide at 75 mg/m²/d with (n = 188) or without (n = 185) adjuvant temozolomide.”

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Combination of Standard-Dose Pembrolizumab With Reduced-Dose Ipilimumab Tolerable and Effective in Advanced Melanoma

Excerpt:

“The combination of the programmed death receptor 1 (PD-1) inhibitor nivolumab at a reduced dose (1 mg/kg) with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab at standard dose (3 mg/kg) for four doses followed by standard-dose nivolumab alone is a standard of care for patients with advanced, previously untreated melanoma. This is based on results from the phase III CheckMate-067 trial that confirmed combination therapy is significantly more effective than single-agent nivolumab or ipilimumab. However, improvement in efficacy is associated with increased treatment-related grade 3/4 adverse events and treatment discontinuation in nearly 40% of patients.”

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Early Chemo Linked to Improved PFS in High-Volume Metastatic Prostate Cancer

Excerpt:

“Patients with high-volume, castration-naïve metastatic prostate cancer may have superior progression-free survival (PFS) outcomes when treated with early docetaxel, according to findings published online in the European Journal of Cancer.

“Using the Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) method, investigators also determined that the benefits associated with androgen deprivation therapy (ADT) plus docetaxel outweighed the risks associated with the treatment.”

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Sacituzumab Govitecan Demonstrates Durable Responses in Metastatic TNBC

Excerpt:

“Sacituzumab govitecan (IMMU-132) was well tolerated and demonstrated early and durable responses in heavily pretreated patients with metastatic triple-negative breast cancer (mTNBC), according to the results of a recent phase I/II study published in the Journal of Clinical Oncology.

“Sacituzumab govitecan is an antibody–drug conjugate that targets Trop-2, which is expressed in more than 90% of TNBCs, by selectively delivering SN-38, the active metabolite of irinotecan. It was granted a breakthrough therapy designation by the FDA in February 2016 for the treatment of patients with mTNBC, following at least 2 treatments for metastatic disease.”

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Neoadjuvant T-DM1 Improves pCR in HER2+/HR+ Early Breast Cancer

Excerpt:

“Twelve weeks of neoadjuvant T-DM1 (ado-trastuzumab emtansine; Kadcyla) with or without endocrine therapy induced superior pathologic complete response (pCR) compared with trastuzumab (Herceptin) plus endocrine therapy in patients with HER2-positive/HR-positive early breast cancer, according to findings recently published online in theJournal of Clinical Oncology.

“In the prospective, neoadjuvant phase II ADAPT trial conducted by the West German Study Group, pCR was 41.0% for patients assigned to T-DM1 alone and 41.5% for those who received T-DM1 and endocrine therapy. In contrast, 15.1% of patients assigned to trastuzumab and endocrine therapy had a pCR (P<.001).”

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Better Results in NSCLC with Higher Dose of ALK Inhibitor

Excerpt:

“Doubling the dose of the ALK inhibitor brigatinib (Alunbrig) improved outcomes in patients with crizotinib (Xalkori)-refractory non-small cell lung cancer (NSCLC), a dose-comparison study showed.

“Patients who started treatment at 90 mg/day and titrated to 180 mg/day had improved response rate (54% versus 45%) and progression-free survival (PFS) as compared with those who received 90 mg throughout the treatment period. Response in brain metastases improved by 50% with the higher dose.”

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Targeted Radiotherapy Limits Side Effects of Breast Cancer Treatment

Excerpt:

“Breast cancer patients who have radiotherapy targeted at the original tumour site experience fewer side effects five years after treatment than those who have whole breast radiotherapy, and their cancer is just as unlikely to return, according to trial results published* in The Lancet (link is external) today (Wednesday).

“The Cancer Research UK-funded IMPORT LOW trial** revealed that five years after treatment, almost all patients were disease free.***

“The researchers at 30 radiotherapy centres across the UK, led by The Institute of Cancer Research, London(link is external), and the Cancer Research UK Cambridge Centre(link is external), studied more than 2,000 women aged 50 or over who had early stage breast cancer that was at a low risk of coming back.”

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