“Shorter time to initiation of adjuvant chemotherapy may reduce relapse and improve outcomes in patients with rapidly proliferating early breast cancer, according results of a phase 3 study.
“Earlier chemotherapy may improve OS and DFS in patients with certain subtypes of breast cancer that are rapidly proliferating and aggressive, such as triple-negative or HER-2–positive disease.
“Alberto Farolfi, a medical oncologist in training at the Scientific Institute of Romagna for the Study and Treatment of Cancer in Meldola, Italy, and colleagues sought to examine the influence of time to chemotherapy on the outcome of these patients and to set a threshold value for time to chemotherapy to better define the clinical outcome.”
“Limited resection is not equivalent to lobectomy when used to treat older patients with stage IA lung cancer of invasive cell types, namely invasive adenocarcinoma and squamous cell carcinoma, a population-based study has now determined.
” ‘Tumor histology in early-stage lung cancer is an important predictor of survival and has therapeutic implications,’ Veluswamy said in an interview. ‘Patients with relatively indolent tumors such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have excellent survival following resection and are therefore likely to benefit from parenchymal sparing provided by limited surgical approaches.’ “
“Post-operative radiation therapy (PORT) is associated with improved overall survival in patients with incompletely resected stage II or III non-small cell lung cancer (NSCLC,) a review of a large population-based cohort from the National Cancer Data Base indicated.
“In the Journal of Clinical Oncology, Byunghoon Yu, MD, Therapeutic Radiology, Yale School of Medicine, and colleagues reported that although the use of PORT has been on the decline, “our findings strongly support the delivery of PORT in patients with incompletely resected NSCLC.”
“They noted the absence of randomized trials evaluating the use of PORT for this patient population and said that unknown confounders, such as surgical quality and patient motivation, may also be present. ‘As such, our analysis, although robust, should be confirmed using other data sets,’ said Yu.
“In the retrospective survival analysis, 3,395 patients with pathologic stage N0-N2, overall American Joint Committee on Cancer stage II or II NSCLC from 2003 to 2011 were identified. All had undergone a lobectomy or pneumonectomy with positive surgical margins.”
“Sequential doxorubicin plus cyclophosphamide followed by weekly paclitaxel is a reasonable adjuvant treatment option for triple-negative breast cancer, according to 12-year follow-up of the Eastern Cooperative Oncology Group’s E1199 phase III trial evaluating optimal taxane type and scheduling in operable breast cancer.
“No similar benefits were observed for patients with hormone receptor-positive tumors or disease not overexpressing HER-2, and obesity and black race were found to be independently associated with recurrence and death, reported investigators online in the Journal of Clinical Oncology.
” ‘Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease,’ wrote multicenter researchers led by Joseph A. Sparano, MD, a medical oncologist at Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, N.Y.
“Updating their 5-year findings, they reported on almost 5,000 eligible women with stage II-III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide. The four-arm trial then randomly assigned them to receive paclitaxel or docetaxel on a standard schedule every three weeks for four doses, or weekly for 12 doses using a 2 x 2 factorial design, with the regimens designated as P3, P1, D3, and D1, respectively. The primary endpoint was disease-free survival (DFS).”
“In a phase III trial (ABCSG-18) reported in The Lancet, Gnant et al found that adjuvant denosumab (Xgeva) reduced the risk of clinical fracture in women with breast cancer receiving aromatase inhibitor therapy.
“In the double-blind study, 3,420 women from Austria and Sweden with early hormone receptor–positive breast cancer receiving aromatase inhibitors were randomized between December 2006 and July 2013 to receive subcutaneous denosumab 60 mg (n = 1,711) or placebo (n = 1,709) every 6 months.
“The primary endpoint was time to first clinical fracture on intention-to-treat analysis. Patients were treated until the prespecified number of 247 first clinical fractures was reached.
“Patients had a median age of 64 years. At baseline, 55% had normal total lumbar spine bone mineral density (T score ≥ –1.0), and the remainder had T scores lower than –1.0. Overall, 16% of patients started aromatase inhibitor therapy at the time of randomization, with the remainder having been on treatment for a median of 1 month prior to randomization. In total, 25% of patients had also received (neo)adjuvant chemotherapy.”
“Amgen AMGN 0.49% today announced results from a randomized, double-blind, placebo-controlled, multicenter Phase 3 study evaluating the treatment effect of adjuvant Prolia® (denosumab), 60 mg once every six months, therapy in postmenopausal women with early hormone receptor positive (HR+) breast cancer receiving aromatase inhibitor therapy. The trial met its primary endpoint of time from randomization to first clinical fracture (HR=0.5, 95 percent CI 0.39-0.65, p<0.0001). The observed 50 percent reduction in fractures between the Prolia and placebo arms, 92 versus 176, respectively, was similar in patients with normal bone health at baseline (n=1,872, HR=0.44, p<0.0001) and in patients who started the trial with early signs of bone loss (n=1,548, HR=0.57, p=0.0021). The data will be presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago today at 9:12 a.m. CT (abstract no. 504). In addition to the presentation, the paper was published online by The Lancet.
“This is the first Prolia trial to enroll patients independent of baseline bone mineral density (BMD) and with the majority in the normal BMD range. The study, which enrolled a total of 3,425 patients, was conducted by the Austrian Breast and Colorectal Cancer Study Group (ABCSG).
” ‘Fracture is a common side effect of aromatase inhibitors, which are an important first-line therapy for postmenopausal women with non-metastatic breast cancer,’ said principal investigator Michael Gnant, professor of surgery at Medical University of Vienna. ‘These encouraging data demonstrate the potential benefit of initiating Prolia simultaneously with aromatase inhibitor therapy, regardless of the patient’s baseline BMD, to decrease the risk of fracture.’ “
“The benefit for breast cancer patients treated with Puma’s neratinib was ‘awfully small’ for a drug that causes ‘a lot of diarrhea,’ said Dr. Harold Burstein, a breast cancer expert from the Dana-Farber Cancer Institute.
“Puma shares are down more than 9% to $177.04 in Monday trading.
“Burstein spoke to me following presentation of results from the neratinib phase III ‘ExteNet’ study at the American Society of Clinical Oncology (ASCO) annual meeting Monday. Puma is developing neratinib for the treatment of HER2-positive breast cancer patients in the extended adjuvant setting.
“The absolute disease-free survival for neratinib was 93.9% compared to 91.6% for placebo — a difference of 2.3 percentage points. The benefit, while statistically significant, is tough to call clinically meaningful for breast cancer patients given the drug’s toxicity, Burstein said.
“Forty percent of patients treated with neratinib experienced grade 3 diarrhea, which is defined as seven more stools per day, incontinence and hospitalization.
” ‘This is not someone simply eating too many chili peppers and having a single bout of diarrhea,’ said Burstein.”
“The American Society for Radiation Oncology (ASTRO) is issuing a new guideline, “Definitive and adjuvant radiotherapy in locally advanced non-small cell lung cancer: An American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline.” The guideline’s executive summary is published in the May-June issue of Practical Radiation Oncology (PRO), ASTRO’s clinical practice journal. The complete guideline, which cites 35 years of data to help guide current treatment and future research, is available online as an open-access article in PRO. The American Society of Clinical Oncology (ASCO) today issued an endorsement of ASTRO’s guideline.
“ASTRO’s guideline panel included 14 leading lung cancer oncologists in the U.S. and Canada, reviewed 74 studies from English language publications within the PubMed database, published from January 1, 1966 to March 15, 2013. The panel developed five Key Questions on the role of definitive and adjuvant radiation therapy (RT) for locally advanced non-small cell lung cancer (LA NSCLC), which represents nearly one-quarter of all lung cancer patients. In addition to the 74 studies, 27 published clinical practice guideline documents that were relevant to one or more of the five Key Questions were reviewed to ensure the guideline panel obtained all appropriate clinical trial reports.”
“Patients with positive surgical margins after lobectomy and adjuvant radiation for non-small cell lung cancer had an increased risk for death compared with patients who were treated with pneumonectomy without radiation.
“ ‘We have demonstrated that positive margins are not that uncommon and occur in roughly 4% of patients receiving lobectomy for stage I or II non-small cell lung cancer [NSCLC],’ Brian C. Gulack, MD, of Duke University, said during a presentation at the American Association for Thoracic Surgery Annual Meeting. ‘Furthermore, positive margin status is associated with worse overall survival, and among patients with positive margins, adjuvant radiation therapy does not appear to provide a significant long-term survival benefit.’
“Gulack and colleagues analyzed patients with positive margins after lobectomy for stage I and stage II NSCLC from the National Cancer Data Base to determine if adjuvant radiation improved survival. Patients who underwent lobectomy without known induction therapy for NSCLC from 1998 to 2006 were grouped by margin status and assessed based on treatment and outcomes.
“Among 50,010 patients who met study criteria, 3.9% had positive margins after lobectomy. Positive margins were associated with an increased risk for death (adjusted HR = 1.46; 95% CI, 1.39-1.6).”