Older Early-Stage NSCLC Patients Benefit From Adjuvant Chemotherapy

“A retrospective study found that early-stage non–small-cell lung cancer (NSCLC) patients over 70 years old derive a similar benefit as younger patients from adjuvant chemotherapy following surgical resection. This suggests that age should not preclude patients from receiving adjuvant chemotherapy.

“ ‘Studies conducted in the last decade have provided evidence that adjuvant chemotherapy after surgical resection improves outcomes for patients with resected stages II and IIIA disease and selected patients with stage I (large tumor size) NSCLC,’ wrote study authors led by Apar Kishor Ganti, MD, of the University of Nebraska Medical Center in Omaha. These studies, however, have not focused specifically on elderly patients, and NSCLC has a median age of 70 years at diagnosis.

“The new study was a population-based retrospective review of 7,593 patients with stage IB to stage III NSCLC who underwent surgical resection; 2,897 (38%) were aged at least 70 years. Results of the study were published online ahead of print in Cancer.

“Among the younger patients, 31.6% received adjuvant chemotherapy, while only 15.3% of the older patients received this treatment (P .0001). Both groups saw changes in rates of adjuvant chemotherapy over time, though of different magnitudes: 9.3% of younger patients diagnosed between 2001 and 2003 received adjuvant chemotherapy, which rose by 27.8% by 2009 to 2011. In older patients, the rate was 4.5% in the earlier period and increased by 16.0%. The most common chemotherapy option used in all patients (64.6%) was carboplatin-based doublets.”

Italian Trial Shows Benefit of Dose-Dense Adjuvant Therapy With Sequential Epirubicin-Cyclophosphamide-Paclitaxel in Early Node-Positive Breast Cancer

“In an Italian 2×2 phase III trial reported in The Lancet, Del Mastro et al found that dose-dense adjuvant therapy with sequential epirubicin, cyclophosphamide, and paclitaxel (EC-P) with or without fluorouracil (5-FU) increased disease-free survival vs standard-interval therapy in early-stage node-positive breast cancer. No benefit of adding 5-FU to EC-P was observed.

“In this open-label trial, 2,091 patients from 81 Italian centers were randomly assigned 1:1:1:1 between April 2003 and July 2006 to receive adjuvant dose-dense chemotherapy every 2 weeks with pegfilgrastim (Neulasta) support with 5-FU plus EC-P (FEC-P, n = 500) or EC-P (n = 502) or standard-interval chemotherapy every 3 weeks with FEC-P (n = 544) or EC-P (n = 545). The primary endpoint was disease-free survival in the intention-to-treat population, with primary comparisons between every-2-week vs every-3-week schedules and FEC-P vs EC-P.

“Overall, patients had a median age of 51 to 53 years, 47% to 55% were postmenopausal, 59% to 63% had lumpectomy, 48% to 52% had T1 tumors, 57% to 64% had one to three positive nodes, 43% to 49% had grade 3 tumors, 21% to 24% were HER2-positive, 77% to 81% were estrogen or progesterone receptor–positive, and 43% to 50% had ≥ 20% Ki67-positive cells.

“The investigators concluded: ‘In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome.’ ”

Radiation after Prostatectomy: Sooner May Be Better

“Important news for men receiving treatment for prostate cancer: Two new studies from the University of Virginia School of Medicine have upended the widely held view that it’s best to delay radiation treatment as long as possible after the removal of the prostate in order to prevent unwanted side effects.

” ‘The common teaching has been, without clear evidence, that urinary incontinence and erectile function are worse when radiation is delivered earlier rather than later, but we didn’t see any protective effect of delayed radiation compared to earlier radiation,’ said radiation oncologist Timothy N. Showalter, MD, of the UVA Cancer Center. ‘It contradicts the clinical principle of delaying radiation as long as possible for the sake of the patient’s side effects. It really speaks against that, and that ought not to be used for a reason to delay radiation.’

“The findings inject hard facts into a debate that has long divided the medical community, with many radiation oncologists preferring adjuvant therapy – radiation given soon after prostate removal to kill off any remaining cancer cells – and many urologists preferring salvage therapy – radiation given later, when prostate-specific antigen tests suggest it’s needed. ‘Urologists tend to prefer to forgo adjuvant radiation therapy, because they fear the side effects, and radiation oncologists tend to prefer offering adjuvant radiation therapy because they fear the risk of metastasis [cancer spreading to other sites in the body],’ Showalter said.”

Puma Biotechnology Initiates Phase II Trial of PB272 in Early Stage HER2-Positive Breast Cancer

“Puma Biotechnology, Inc. PBYI, +2.74% a development stage biopharmaceutical company, announced the initiation of a Phase II trial of Puma’s investigational drug PB272 (neratinib) for the extended adjuvant treatment of breast cancer.

“The 70 patient study will be an open label single arm Phase II trial of PB272 monotherapy administered to patients with HER2-positive early stage breast cancer who have previously received adjuvant treatment with trastuzumab. Patients will receive extended adjuvant treatment with neratinib for a period of one year. Patients will receive primary prophylaxis with high dose loperamide (16 mg per day initially) in order to attempt to reduce the neratinib-related diarrhea. The primary endpoint of the trial is reduction in the incidence and severity of diarrhea.

“ ‘We are pleased to initiate this Phase II trial,’ said Alan H. Auerbach, Chief Executive Officer and President. ‘Because the ExteNET Phase III trial was run prior to the implementation of loperamide prophylaxis in clinical trials of neratinib, in the ExteNET Phase III trial neratinib was administered without loperamide prophylaxis. The results from this Phase II study will give us a better understanding of the safety of neratinib in the extended adjuvant setting with concurrent high dose loperamide administered and, importantly, to what degree the grade 3 neratinib-related diarrhea can be reduced. We anticipate that initial results from this trial should be available by yearend 2015 and would enable us to include this data in our NDA filing for neratinib in the extended adjuvant setting, which is currently anticipated for the first quarter of 2016.’ “

Ipilimumab Is on the Way to Approval for Stage III Melanoma Treatment

“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 Are Common for Women Undergoing Chemotherapy for Early Stage Breast Cancers

“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 Lung Cancer Outcomes in Older Patients

“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.”

ADT Before or After Surgery Gives Similar Survival Rates in Prostate Cancer

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.”

Profiling Immune System Genes Could Predict Benefit of Adjuvant Trastuzumab in Early-Stage HER2-Positive Breast Cancer

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.”