Some Benefit Seen for Weekly Adjuvant Paclitaxel in Triple-Negative Breast Ca (CME/CE)

“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).”

Denosumab Reduces Clinical Fracture Risk in Postmenopausal Women Receiving Aromatase Inhibitors

“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 Presents Phase 3 Data At ASCO Showing Prolia Significantly Reduced Bone Fractures In Breast Cancer Patients Receiving Aromatase Inhibitors

“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.’ “

Puma Bio Breast Cancer Drug Given Rough Treatment at ASCO '15

“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.”

ASTRO Issues Guideline on Definitive and Adjuvant RT for Locally Advanced Non-Small Cell Lung Cancer

“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.”

Stage I and II NSCLC: Removal of Whole Lung Could Work Better than Removal of Cancerous Lobe Followed by Radiation

“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).”

Adjuvant Chemotherapy Associated with Shorter Survival in LCNEC

“Patients who underwent adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinomas demonstrated poorer 3-year survival than those who did not undergo adjuvant treatment, according to study results presented at the American Association for Thoracic Surgery Annual Meeting.

“ ‘We did not see any particular subset of patients who may benefit from this treatment,’ researcher Pier Luigi Filosso, MD, of the University of Torino in Italy, said during a presentation.

“Filosso and colleagues conducted a retrospective cohort study to determine the impact of adjuvant chemotherapy in patients with resected large cell neuroendocrine carcinomas (LCNEC). The analysis included 400 patients with LCNEC who underwent surgery between 1992 and 2014 at one of 14 institutions worldwide.

“Researchers used the Kaplan-Meier method to estimate OS after resection. Propensity score for the likelihood of receipt of adjuvant chemotherapy was estimated based on patient age, gender, prior malignancy, ECOG performance status, TNM stage and year of surgery.”

NRAS & BRAF Mutational Status May Help Guide Therapy in Melanoma Patients

“A new study is suggesting that it may be important to look at mutational status when determining adjuvant treatments for melanoma patients. Researchers at the University of North Carolina (UNC) School of Medicine are now reporting that NRAS and BRAF mutations in melanoma patients should be identified early, and may need to be taken into consideration when establishing treatment paradigms.

“The results of this study were published online in the April 9, 2015 issue of JAMA Oncology.

“Researchers looked at data from the Genes, Environment, and Melanoma (GEM) Study, which included 912 patients with a median follow-up of 7.6 years. They examined tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status.  They found 13% of the patients had tumors with NRAS mutations, 30% had BRAF mutations, and 57% had neither.

“There was no statistically significant difference in the 5-year survival rates for patients with NRAS or BRAF-mutated melanoma tumors compared with survival in those patients with tumors lacking mutations. However, there were lower 5-year survival rates for patients with higher-risk tumors with mutations. The study suggested the 5-year survival rate was 73% for patients with high-risk NRAS-mutated tumors, 71% for patients with high-risk tumors with BRAF mutations, and 82% for patients with high-risk cancer and lacking either mutation.”

Ipilimumab Improves Survival in High-Risk Stage III Melanoma After Surgery

“Results of an EORTC trial appearing in The Lancet Oncology show that adjuvant Ipilimumab significantly improves recurrence-free survival in patients with completely resected stage III melanoma at high risk of disease recurrence, but that this treatment was also associated with a high rate of immune-related adverse events.

“Prof Alexander M M Eggermont of the Gustave Roussy Cancer Campus and lead author of this study says, ‘Ipilimumab has already been approved as a treatment for patients with advanced melanoma. Our intention with this study was to assess Ipilimumab as an adjuvant treatment for patients with completely resected stage III melanoma at high risk of recurrence. In my experience, this marks both the first clinical trial of an approved drug with an effect on survival in advanced melanoma in the adjuvant setting, and, in this same setting, the first to study an immune checkpoint inhibitor in the adjuvant setting. Our results show that Ipilimumab is active in the adjuvant setting, but the side-effects are considerable.’

“Between 2008 and 2011, the double-blind, phase III EORTC trial 18071 accrued 951 patients who were randomly assigned to receive either Ipilimumab (475 patients) or placebo (476 patients). All patients were included in the intention-to-treat analyses. At a median follow-up of 2.74 years, the median recurrence-free survival was 26.1 months (95% confidence interval (CI) 19.3 – 39.3) in the Ipilimumab group and 17.1 months (95% CI 13.4 – 21.6) in the placebo group (hazard ratio 0.75; 95% CI 0.64 – 0.90; p = 0.0013). The 3-year recurrence-free survival rate was 46.5% (95% CI 41.5 – 51.3) in the Ipilimumab group and 34.8% (30.1 – 39.5) in the placebo group.”