Adding Ziv-Aflibercept to Topotecan Improves Progression-Free Survival but Increases Toxicity in Platinum-Treated Small Cell Lung Cancer

Editor’s note: A recent clinical trial with volunteer patients tested whether a treatment that combines a drug called ziv-aflibercept (Zaltrap) with the drug topotecan would be better than toptecan alone for people with small cell lung cancer (SCLC). All participating patients had previously been treated with platinum-based chemotherapy and had been treated for brain metastases. Patients were randomly assigned to be treated with either topotecan alone, or the topotecan/ziv-aflibercept combination. The researchers found that the combination treatment significantly increased the number of patients who survived three months or more without their disease worsening. However, the combo treatment had worse side effects and did not improve overall survival.

“The phase II Southwest Oncology Group (SWOG) S0802 trial reported in the Journal of Clinical Oncology by Allen et al showed that adding ziv-aflibercept (Zaltrap) to topotecan improved 3-month progression-free survival, but increased toxicity and had no effect on overall survival, in patients with platinum-treated small cell lung cancer (SCLC)…

“In the trial, 189 patients who had experienced disease progression after one line of platinum-based chemotherapy and had treated brain metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, and no recent vascular events or bleeding diatheses were randomly assigned to receive weekly topotecan at 4 mg/m2 with (n = 97) or without (n = 92) ziv-aflibercept at 6 mg/kg every 21 days. Patients were stratified as platinum-refractory (n = 55 vs 51) or platinum-sensitive (n = 42 vs 41). Progression-free survival at 3 months was the primary endpoint.”


Prophylactic Cranial Irradiation Increased DFS in Patients with Stage III NSCLC

Editor’s note: People who are at risk of having their cancer spread (metastasize) to the brain can receive “prophylactic cranial irradiation” to help prevent it. In this procedure, the head is treated with radiation to kill any cancer cells that may have already spread there but are not yet detectable. A recent study investigated the benefits of prophylactic cranial irradiation for people with fully resected (surgically removed), stage IIIA N2 non-small cell lung cancer (NSCLC). The study involved volunteer patients at high risk of brain metastases whose lung tumors had been surgically removed and who had received post-surgery chemotherapy to keep the cancer from returning. Some of the patients were given prophylactic cranial irradiation, and some were not. The researchers found that patients who received prophylactic cranial irradiation had a decreased risk of brain metastases and also had a longer period of survival without return of their cancer.

Excerpt:

“Prophylactic cranial irradiation prolonged disease-free survival and decreased the incidence for brain metastases in patients with fully-resected stage IIIA N2 non–small cell lung cancer at high-risk for cerebral metastases after completing adjuvant chemotherapy, according to results presented at the ASCO Annual Meeting.

“Si-Yu Wang, MD, of the department of thoracic surgery at the Sun Yat-sen University Cancer Center in China and colleagues assessed whether prophylactic cranial irradiation improves survival in this population of patients.

“Between 2005 and 2009, researchers randomly assigned 156 patients to 30 Gy prophylactic cranial irradiation in 10 fractions (n=81) or observation (n=75). DFS served as the primary outcome measure; secondary outcome measures included the incidence for brain metastases, OS and adverse events. The study was halted early due to slow accrual.

“Patients treated with prophylactic cranial irradiation experienced a decreased risk for brain metastases (5-year brain relapse rate, 13.6% vs. 41.3%; OR=0.223; 95% CI, 0.102-0.489).

“DFS was significantly higher in patients assigned prophylactic cranial irradiation (28.5 months) compared with controls (21.2 months; HR=0.67; 95% CI, 0.46-0.98). Three-year DFS was 42% and 5-year DFS was 26.1% in the prophylactic cranial irradiation group vs. 29.8% at 3 years and 18.5% at 5 years for controls.”


ASCO Clinical Practice Guideline: Systemic Therapy for Patients With Advanced HER2-Positive Breast Cancer

“Approximately 15% of patients with breast cancer have tumors that overexpress the HER2 protein and these patients can benefit from HER2-targeted therapies. The American Society of Clinical Oncology recently released a clinical practice guideline on systemic therapy for patients with advanced HER2-positive breast cancer, published in the Journal of Clinical Oncology. The rationale for the guideline is that several new agents have become available for treatment of metastatic HER2-positive breast cancer since the approval of trastuzumab (Herceptin).

“Up to half of all patients with HER2-positive metastatic breast cancer develop brain metastases over time. Recommendations for the management of brain metastases in patients with HER2-positive breast cancer are detailed in another recently released companion guideline.”

Editor’s note: Click through to the full article (arrow button to the right of the title) to see the recommendations.


Brain Metastases in Melanoma Require Multidisciplinary Approach

Brain metastases are responsible for the majority of mortality and morbidity among patients with melanoma, and a multidisciplinary approach is necessary to effectively manage this complication, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

“ ‘This subject has not been well studied. This is the question that people didn’t want to address, but now people are taking on this task,’ Geoffrey T. Gibney, MD, a medical oncologist in the department of cutaneous oncology at Moffitt Cancer Center, said during a presentation.”

Editor’s note: This article is a good summary of brain metastasis in melanoma.


Combo Chemotherapy Bests Single Drug Against Melanoma

Two chemotherapy drugs may be better than one against melanoma, according to results from an ongoing clinical trial that were presented at the 2013 meeting of the  International Society for Melanoma Research. The drugs were dacarbazine, which is U.S. Food and Drug Administration (FDA)-approved for melanoma, and paclitaxel, which is FDA-approved for breast, lung, and pancreatic cancers. In a phase III trial of 529 melanoma patients, the drug combination kept tumors from growing two times longer than dacarbazine alone (4.8 vs 2.5 months, respectively). The subgroups that did best included men and people with melanomas that had spread to the liver or brain. This is particularly encouraging for the latter group because they have the worst prognosis.


Combination of BRAF Inhibitors and Brain Radiotherapy in Patients With Metastatic Melanoma Shows Minimal Acute Toxicity

“TO THE EDITOR: Recently, Satzger et al reported increased skin toxicity within the irradiated field of patients with melanoma concomitantly receiving BRAF inhibitors and radiotherapy for extracranial metastases. Our data indicate that toxicity on the skin or brain is not a limiting factor for combining BRAF inhibitor treatment and irradiation of brain metastases.”


Checkpoint Modulation in Melanoma: An Update on Ipilimumab and Future Directions

“Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, was the first therapy demonstrated to improve overall survival in melanoma. Since ipilimumab’s approval by the FDA in 2011, a wealth of data has amassed, helping clinicians to optimize its use. We have learned how to mitigate the adverse effects of ipilimumab, identified its effects in melanoma subpopulations such as those with brain metastases, uveal melanoma, and mucosal melanoma, discovered potential biomarkers of activity, and investigated its use in combination with other therapeutic modalities. These discoveries have paved the way for rapid development of second-generation immunomodulatory antibodies such as inhibitors of the programmed cell death 1 receptor axis. These new agents hold promise as monotherapy, but perhaps the greatest allure lies in the possibility of combining these agents in synergistic multidrug regimens.”


Approved Immunotherapy Extends Life After Melanomas Have Spread to the Brain

An FDA-approved immunotherapy was thought to be too risky for people with melanomas that have spread to the brain—but a new study suggests otherwise. The therapy is high doses of interleukin-2, an immune system booster that can have nasty side effects, including seizures and abnormal heart rhythms. In a review of eight melanoma patients with tumors in their brains, this treatment doubled the average survival from 4 months to more than 8 months. The researchers call for extending use of this immunotherapy to melanoma patients with brain metastases.


Survival Patterns Following Brain Metastases for Patients with Melanoma in the Targeted Therapy Era

“Survival from metastatic melanoma (MM) has been significantly prolonged with the introduction of molecularly targeted therapy, including BRAF inhibitors (BRAFi) for patients (pts) with the V600E mutation. Here, we present the first data describing patterns of survival after diagnosis of brain metastases (BM) in a large cohort of these pts with long follow-up.”