tnAcity Data Presented at SABCS Evaluates the Investigational Use of ABRAXANE® as First-Line Treatment of Metastatic Triple Negative Breast Cancer

Excerpt:

“Celgene Corporation (CELG) today announced that the results of its randomized phase II tnAcity trial of ABRAXANE® for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) December 6-10, 2016. The trial found that an investigational weekly combination regimen of ABRAXANE + carboplatin had significantly longer progression-free survival (PFS) (7.4 months) compared to weekly regimens of either ABRAXANE + gemcitabine (5.4 months) or of carboplatin + gemcitabine (6.0 months) as first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC).”

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Patients With EGFR Expressing NSCLC Benefit Most From Necitumumab Added to Chemotherapy

Excerpt:

“Patients with epidermal growth factor receptor (EGFR) expressing advanced squamous non-small-cell lung cancer benefit most from necitumumab added to gemcitabine and cisplatin chemotherapy, according to a subgroup analysis from the SQUIRE trial presented today at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.

“The randomised phase III SQUIRE trial demonstrated that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improved overall survival in patients with stage IV squamous  by 1.6 months compared to chemotherapy alone. The current study analysed outcomes in the subgroup of patients with EGFR expressing tumours compared to those with no EGFRs.”

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TS Expression Could Guide Treatment in Nonsquamous NSCLC

“The combination of pemetrexed and cisplatin was superior to gemcitabine and cisplatin only in those non-squamous non–small-cell lung cancer (NSCLC) patients who were negative for the enzyme thymidylate synthase (TS), suggesting it could be used as a predictive marker to guide treatment.

“Previous research has shown that pemetrexed/cisplatin offers superior survival in nonsquamous NSCLC, while gemcitabine/cisplatin was better in squamous NSCLC. “A plausible mechanism for the histotype-dependent efficacy of pemetrexed-based chemotherapy can be explained by the presence of different levels of TS according to histologic types, with adenocarcinoma of lung cancer exhibiting a lower TS protein expression level than squamous cell carcinoma or neuroendocrine carcinoma,” wrote study authors led by Myung-Ju Ahn, MD, PhD, of Sungkyunkwan University School of Medicine in Seoul.

“TS is involved in de novo DNA synthesis, and inhibiting the enzyme leads to arrested cell proliferation; pemetrexed’s antitumor effects arise from inhibition of TS. The new study’s results were published online ahead of print in the Journal of Clinical Oncology.”


Addition of Necitumumab to First-Line Gemcitabine-Cisplatin Improves Overall Survival in Stage IV Squamous NSCLC

“In the phase III SQUIRE trial reported in The Lancet Oncology, Thatcher et al found that the addition of the second-generation epidermal growth factor receptor (EGFR) antibody necitumumab to first-line gemcitabine-cisplatin improved overall survival among patients with stage IV squamous non–small cell lung cancer (NSCLC).

“In this open-label trial, 1,093 patients from 26 countries were randomly assigned between January 2010 and February 2012 to receive gemcitabine-cisplatin with (n = 545) or without (n = 548) necitumumab. Necitumumab 800 mg was given intravenously on days 1 and 8 of 3-week cycles and continued after the end of chemotherapy until disease progression or intolerable toxicity. Gemcitabine 1,250 mg/m² was given on days 1 and 8, and cisplatin 75 mg/m² was given on day 1 of 3-week cycles. Randomization was stratified by Eastern Cooperative Oncology Group (ECOG) performance status and geographic region. The primary endpoint was overall survival in an intent-to-treat analysis.

“For the necitumumab and control groups, the median age was 62 years in both; 83% and 84% of patients were male; 84% and 83% were white; the geographic region was North America, Europe, or Australia for 87% in both South America, South Africa, or India for 6% in both, and Eastern Asia for 8% and 7%; Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 30% and 33%, 1 in 61% and 58%, and 2 in 9% in both; and 55% in both had metastatic disease involving more than two organ systems.”


Combining Chk1 Inhibition with Standard Dose Gemcitabine May Be Safe and Effective

“Adding the investigational agent GDC-0425, which blocks the function of a protein called checkpoint kinase 1 (Chk1), to standard doses of the chemotherapy drug gemcitabine, was safe and yielded responses in patients with a variety of cancer types, including triple-negative breast cancer, melanoma, and cancer of unknown primary, according to data from a phase I clinical trial presented at the AACR Annual Meeting 2015, held April 18-22.

” ‘Gemcitabine is a chemotherapy agent that works by damaging the DNA of cancer cells while they are dividing to form more cancer cells,’ said Jeffrey R. Infante, MD, director of the drug development program at Sarah Cannon Research Institute in Nashville, Tennessee. ‘Sometimes cancer cells pause during the process of cell division and the cell has time to repair the DNA damage caused by gemcitabine, making the drug less effective. Chk1 is a protein kinase that can trigger this pause, and the idea underpinning our trial was that blocking Chk1 with GDC-0425 might prevent cancer cells from having time to repair gemcitabine-damaged DNA.

” ‘We were excited to find that we could safely combine GDC-0425 with the standard 1000 milligram per m2 dose of gemcitabine because we had been concerned that this combination might not be tolerable,’ continued Infante. ‘We are also encouraged to see responses in patients with a variety of cancer types. The results have given us a good platform for moving forward with Chk1 inhibitor/gemcitabine combination therapy for further study.’ “


Cisplatin plus Gemcitabine Improves Outcomes in Metastatic Triple-Negative Breast Cancer

“Cisplatin plus gemcitabine demonstrated superior PFS outcomes compared with paclitaxel plus gemcitabine for women with metastatic triple-negative breast cancer, according to results of a randomized phase 3 study.

“ ‘Despite general improvements in the management of breast cancer, triple-negative breast cancer represents a continuing challenge because, when compared with other subtypes, it is associated with a higher frequency of recurrence, shorter DFS and poor OS, despite similar therapeutic approaches to other breast cancers,’ Xi-Chun Hu, MD, of the department of medical oncology at the Fudan University Shanghai Medical College, and colleagues wrote. ‘The median distant disease-free interval for relapsed triple-negative breast cancer is about 1 to 2 years and the median survival for metastatic triple-negative breast cancer is about 1 year.’

“Hu and colleagues evaluated data from 236 patients (median age, 47 years) from 12 institutions or hospitals within the Chinese Breast Cancer Study Group. Patients had not undergone previous chemotherapy for metastatic disease and they had an ECOG performance status of 0 to 1.

“Researchers randomly assigned patients 1:1 to a chemotherapy regimen of 1,250 mg/m2 gemcitabine on days 1 and 8 plus 75 mg/m2 cisplatin or 175 mg/m2 paclitaxel on day 1 for eight 3-week cycles.”


FDA Names New Drug Tarextumab "Orphan Drug" for Small Cell Lung Cancer

The gist: The U.S. Food and Drug Administration (FDA) has granted “orphan drug” designation to a new drug called tarextumab for small cell lung cancer (SCLC) and pancreatic cancer. The designation will make it easier for the drug maker to successfully develop tarextumab and get it to patients in the U.S. Tarextumab has shown promise in patients in a clinical trial. It is given to patients in combination with chemotherapy.

“The US Food and Drug Administration (FDA) has granted orphan drug designation to the OncoMed agent tarextumab for the treatment of pancreatic cancer and lung cancer. Tarextumab (formerly OMP-59R5) is a fully human monoclonal antibody targeting the Notch 2/3 receptors.

“ ‘We are excited to receive two separate orphan drug designations for tarextumab for the treatment of pancreatic and small-cell lung cancer,’ said Paul J. Hastings, OncoMed’s chairman and chief executive officer, in a statement.

“Earlier this month the drug company announced final phase 1b clinical and biomarker data from the ALPINE (Antibody Therapy in First-Line Pancreatic Cancer Investigating Anti-Notch Efficacy and Safety) study, which tested tarextumab in combination with gemcitabine plus nab-paclitaxel in pancreatic cancer.

“Of the 29 patients in the trial, 21 (73%) achieved either a partial response or stable disease with the combination therapy.”


Thymidylate Synthase Predicts Response to Chemo in NSCLC

The gist: Scientists have found that measuring a patient’s levels of a protein called thymidylate synthase (TS) could predict how well different kinds of chemotherapy might work for treating non-small cell lung cancer (NSCLC). Specifically, patients with low-levels of TS benefitted more from treatment with cisplatin plus pemetrexed than with cisplatin plus gemcitabine.

“A new phase II study suggests that expression of the enzyme thymidylate synthase (TS) can be used as a predictive marker for patients with non–small-cell lung cancer undergoing chemotherapy. Benefits of cisplatin plus pemetrexed over cisplatin plus gemcitabine were more pronounced in TS-negative patients than in TS-positive patients.

“ ‘Thymidylate synthase,’ said Myung-Ju Ahn, MD, of Sungkyunkwan University School of Medicine in Seoul, in a press release, ‘is targeted by pemetrexed, which is the most widely used chemotherapeutic regimen in the treatment of non-squamous NSCLC.’ Previous work has shown that the cisplatin/pemetrexed combination is superior to cisplatin/gemcitabine in non-squamous NSCLC, but levels of TS could predict the level of response.

“In this study, 315 non-squamous NSCLC patients were first stratified as either TS-positive (more than 10% of tumor cells express TS) or TS-negative, and then randomized to cisplatin plus either pemetrexed or gemcitabine. Results were presented at the European Society of Medical Oncology (ESMO) 2014 Congress in Madrid.

“The objective response rate in the cisplatin/pemetrexed patients who were TS-negative was 47%, compared with 21.1% in the cisplatin/gemcitabine group. In the TS-positive patients, meanwhile, the objective response rates were 40.3% for cisplatin/pemetrexed patients and 39.2% for cisplatin/gemcitabine patients (P = .008).”


NICE 'No' for Celgene's Abraxane in Pancreatic Cancer

The National Institute for Health and Care Excellence has published new recommendations rejecting the use of Celgene’s Abraxane (nab-paclitaxel) on the National Health Service to treat patients with advanced pancreatic cancer.

“According to the cost regulator, the drug, a novel formulation of the chemotherapy paclitaxel, is not as effective as standard therapy and is more expensive, and thereby fails to hit value-for-money criteria.

“NICE says that data provided by Celgene show that the chemo regimen FOLFIRINOX, a first-line option for patients with the disease, was actually more clinically effective than the Abraxane/gemcitabine combination. And while Abraxane/gemcitabine was more effective than gemcitabine alone, it resulted in more serious side effects.”