“The FDA has accepted a supplemental Biologics License Application (sBLA) for ipilimumab (Yervoy) as an adjuvant treatment of patients with stage III melanoma at high risk of recurrence following complete resection, according to Bristol-Myers Squibb, the company developing the drug. The FDA is scheduled to make a decision on adjuvant ipilimumab by October 28, 2015.
“The acceptance of the sBLA is based on results from the phase III EORTC 18071 trial, which was presented at the 2014 ASCO Annual Meeting. This study showed a 25% improvement in recurrence-free survival (RFS) in patients treated with ipilimumab versus placebo (HR = 0.75; 95% CI, 0.64–0.90).
“ ‘This is a promising treatment—we saw substantially fewer recurrences among patients who are at high risk of relapse,’ Alexander Eggermont, MD, PhD, director general of the Gustave Roussy Cancer Campus Grand Paris in France, said in an 2014 ASCO Annual Meeting press release. ‘We’ve seen many impressive new treatments for advanced melanoma in recent years. This trial with ipilimumab is the first to show we may be able to give these new drugs earlier in the course of disease, where they can do more good and potentially cure more patients.’ ”
“Emergency room visits and hospitalizations are common among patients with early breast cancer receiving chemotherapy, particularly among those receiving a regimen containing docetaxel, according to a report by Enright et al in the Journal of Oncology Practice. ‘In this population-based cohort study, [emergency room visits and hospitalizations] were significantly higher among women with [early breast cancer] undergoing adjuvant chemotherapy compared with age-matched noncancer controls and compared with themselves 2 years before their cancer diagnosis,’ the authors wrote.
“Patients diagnosed with between January 2007 and December 2009 were identified using the Ontario Cancer Registry. ‘Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up,’ the investigators noted. All patients received one or more cycles of adjuvant chemotherapy.
“A total of 8,359 patients with early breast cancer were matched to the same number of noncancer controls on age, comorbidity, and geographic location. The mean age of the study participants was 53.67 years.
“ ‘[Emergency room visits and hospitalizations] within 30 days of chemotherapy were identified. If the primary reason for the visit was a common chemotherapy toxicity, the visit was considered chemotherapy associated. All-cause and chemotherapy-associated visits were compared between patient cases and controls,’ the authors explained.”
“Adjuvant chemotherapy may improve survival for older patients with stage I non–small cell lung cancer, according to an analysis of the SEER–Medicare database.
“However, the regimen also is associated with serious adverse events, according to an analysis of the SEER-Medicare database.
“Weighing the risks vs. benefits of adjuvant chemotherapy is more difficult in older patients, as they have a greater risk for disease recurrence after surgical resection but also have a more limited life expectancy.
“Jyoti Malhotra, MD, of the department of hematology and oncology at Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, and colleagues conducted a population-based study to compare survival and rates of serious adverse events among elderly patients with T2N0 NSCLC. The analysis included 3,289 patients aged older than 65 years who were treated between 1992 and 2009. All patients had tumors at least 4 cm, and they underwent surgical resection followed by either observation or adjuvant platinum chemotherapy with or without postoperative radiation.”
The gist: Recent research found that prostate cancer patients have similar survival rates whether they have androgen deprivation therapy (ADT) before or after tumor-removal surgery. The study focused on men with intermediate- or high-risk prostate cancer who were treated between 1995 and 2002.
“Patients with intermediate- or high-risk prostate cancer demonstrated similar biochemical relapse-free survival, distant metastasis-free survival and OS regardless of whether they received androgen deprivation in the neoadjuvant or adjuvant settings, according to study results.
“Patients with localized prostate cancer typically undergo androgen deprivation therapy (ADT) in the neoadjuvant setting, concurrent with radiation therapy.
“Michael A. Weller, MD,of Cleveland Clinic, and colleagues assessed whether patients who underwent ADT in the adjuvant setting experienced different outcomes.
“The analysis included 515 patients treated with radiation therapy and ADT from 1995 to 2002. Of these patients, 311 underwent ADT in the neoadjuvant setting, beginning 2 to 3 months before the start of radiation therapy. The other 204 patients underwent ADT in the adjuvant setting, immediately after the completion of radiation therapy.”
The gist: Analyzing genes that affect the activity of a patient’s immune system could help doctors predict how well trastuzumab (Herceptin) will work. Researchers recently analyzed immune system genes in 1,282 HER2-positive tumor samples from patients. They found that patients who had more immune system genes “turned on” survived longer without their cancer returning (recurrence) if they received adjuvant (after-surgery) Herceptin instead of chemotherapy. Patients with fewer active immune system genes did equally well whether they were treated with Herceptin or chemotherapy. These results show that immune system gene profiling could potentially be used to make decisions about how to treat early-stage HER2-positive breast cancer.
“In a study reported in the Journal of Clinical Oncology, Perez et al found that an immune function gene profile was associated with significantly improved relapse-free survival among patients with early-stage HER2-positive breast cancer who had trastuzumab (Herceptin) added to adjuvant chemotherapy in the North Central Cancer Treatment Group (NCCTG) N9831 trial…
“The investigators concluded: ‘Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.’
“They observed: ‘The potential clinical significance of our results, within the context of identification of patients who are likely to benefit (increased [relapse-free survival]) from adjuvant trastuzumab, is considerable. Identification of patients who are unlikely to benefit from trastuzumab on the basis of evaluation of the immune status of the tumor before initiation of therapy may have even greater significance. Patients with low immune function gene expression scores might be enrolled onto trials to test the efficacy of HER2-targeted regimens that combine trastuzumab with some other therapeutic agent. Alternatively, these patients might be the focus of future clinical trials designed to evaluate therapeutic approaches that might enhance the immune activity within HER2-positive tumors and thereby sensitize the tumors to biologic therapies.
“One strategy in this regard cited by the investigators is the inhibition of immune-suppressive signaling pathways—eg, with agents targeting programmed cell death protein (PD-1) or its ligand, PD-L1. Another is to increase immunoreactivity via modification of the immunoglobulin backbone of anti-HER2 antibodies.”
Pertuzumab (Perjeta) is a relatively new drug that targets HER2, a protein found at higher-than-normal levels in about 15% to 20% of all breast cancers. Too much HER2 leads to tumor growth. Currently, all newly diagnosed breast cancer patients have their tumors’ HER2 levels tested. Knowing whether a patient’s HER2 levels are abnormally high (HER2-positive) or normal (HER2-negative) is a major factor in choosing a treatment, thanks to the availability of trastuzumab (Herceptin) and, now, other HER2-targeted drugs such as Perjeta, T-DM1 (Kadcyla), and lapatinib (Tykerb). These drugs are all used to treat HER2-positive patients. Continue reading…
“Outcomes for early-stage breast cancer have improved, but incomplete examination and follow-up may have underestimated subsequent risks for treatment-associated marrow neoplasm in patients who undergo adjuvant therapy, according to study results.
“Prior first-generation adjuvant chemotherapy trials reported a 0.27% cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia after 8 years.
“In the current study — conducted by Antonio C. Wolff, MD, professor of oncology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, and colleagues — the risk for marrow neoplasm among patients who underwent radiation and/or adjuvant chemotherapy for early-stage breast cancer remained low, but was higher than previously described.
“Wolff and colleagues used the National Comprehensive Cancer network Breast Cancer Outcomes Database to evaluate 20,063 patients with stage I to stage III breast cancer treated at US academic centers between 1998 and 2007.”
The gist: After surgery to remove their tumors, women with stage I, HER2-positive breast cancer might benefit from a combination of lower-intensity chemotherapy and the targeted drug trastuzumab (Herceptin). In a clinical trial, patients received post-surgery (adjuvant) treatment with the drugs paclitaxel and Herceptin. After three years, 98.7% were alive and had not experienced return of invasive breast cancer.
“In a phase 2 clinical trial, women with small (stage 1), HER2-positive breast tumors who received a combination of lower-intensity chemotherapy and a targeted drug following surgery were highly unlikely to have the cancer recur within three years of treatment, investigators at Dana-Farber Cancer Institute and other institutions report in a paper published today by the New England Journal of Medicine.
“The findings may help establish the therapy – which combines the chemotherapy agent paclitaxel and the targeted drug trastuzumab (Herceptin) – as the first standard treatment approach for this group of patients, the authors state.
” ‘Many previous studies excluded women with small (less than 2 cm in diameter) HER2-positive breast tumors that hadn’t spread to nearby lymph nodes from clinical trials of trastuzumab, because it wasn’t considered prudent to expose them to an investigational drug, given the relatively low risk that the disease would recur. Without a single, standard treatment for this group of patients, treatment approaches have varied widely. (Breast cancers are classified as HER2-positive if their cells have surplus human epidermal growth factor receptors on their surface, making them extra-sensitive to signals to grow and divide.)”
The gist: A clinical trial compared postmenopausal breast cancer patients who took tamoxifen after surgery with patients who took tamoxifen plus the drug anastrozole. They researchers found that, after three years, more women with lobular breast cancer who took anastrozole were alive than those who took only tamoxifen. These results suggest that anastrozole may benefit postmenopausal women with lobular breast cancer.
“The survival benefit postmenopausal patients with breast cancer derive from anastrozole vs. tamoxifen varies considerably by histology, according to an analysis of phase 3 study results presented at the San Antonio Breast Cancer Symposium.
“Researchers suggested the finding may help refine adjuvant endocrine treatment decisions.
“Several prior studies showed aromatase inhibitors improved outcomes among postmenopausal patients with breast cancer compared with tamoxifen monotherapy. A meta-analysis by Forbes and colleagues, which included data on 11,798 patients included in randomized trials that compared 5 years of tamoxifen vs. a sequence of tamoxifen followed by aromatase inhibitors, showed patients assigned aromatase inhibitors demonstrated a significant reduction in recurrence (RR=0.84; 95% CI, 0.73-0.97). Researchers also observed significantly fewer deaths in the aromatase inhibitor group (RR=0.84; 0.73-0.97)…
“ ‘In summary, among all patients with lobular cancer, anastrozole was associated with a significant reduction in OS events compared to tamoxifen,’ Knauer said. ‘However, anastrozole efficacy was strongly depending on histology and intrinsic subtype of breast cancer.’ ”