Improved Survival for Patients with Brain Mets Who Are 50 and Younger and Receive SRS Alone

“Cancer patients with limited brain metastases (one to four tumors) who are 50 years old and younger should receive stereotactic radiosurgery (SRS) without whole brain radiation therapy (WBRT), according to a study available online, open-access, and published in the March 15, 2015 issue of the International Journal of Radiation Oncology * Biology * Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). For patients 50 years old and younger who received SRS alone, survival was improved by 13 percentage points when compared to those patients 50 years old and younger who received both SRS and WBRT.

“This study, ‘Phase 3 Trials of Stereotactic Radiation Surgery With or Without Whole-Brain Radiation Therapy For 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis,’ analyzed patient data from the three largest randomized clinical trials (RCT) of SRS and WBRT conducted to-date: the Asian trial (JROSG99-1) by Aoyama et al.[1], published in 2006; the North American trial (MDACC NCT00548756) by Chang et al.[2], published in 2009; and the European trial (EORTC 22952-26001) by Kocher et al.[3], published in 2011. A total of 364 patients from the three RCTs were evaluated for this meta-analysis. Of those 364 patients, 51 percent (186) were treated with SRS alone, and 49 percent (178) received both SRS and WBRT. Nineteen percent of patients (68) were 50 years old and younger, and 61 percent (19) of these patients had a single brain metastasis. Twenty percent of all patients (72) had local brain failure, which is the occurrence of progression of previously treated brain metastases; and 43 percent (156) experienced distant brain failure, which is the occurrence of new brain metastases in areas of the brain outside the primary tumor site(s).

“The impact of age on treatment effectiveness revealed SRS alone yielded improved overall survival (OS) in patients 50 years old and younger. Patients 50 years old and younger who received SRS alone had a median survival of 13.6 months after treatment, a 65 percent improvement, as opposed to 8.2 months for patients 50 years old and younger who were treated with SRS plus WBRT. Patients >50 years old had a median survival of 10.1 months when treated with SRS alone, and 8.6 months for those who received SRS plus WBRT.”

Crizotinib Shows Promise against Brain Metastases in Patients with NSCLC

The gist: A drug called crizotinib (Xalkori) has shown promise for some people with non-small cell lung cancer (NSCLC) that has metastasized to the brain. Xalkori is already used to treat NSCLC in patients whose tumors have a genetic abnormality known as “ALK rearrangement.” A recent study focused specifically on people whose NSCLC had spread to the brain. The researchers found that Xalkori may help patients whose brain metastases have not yet caused any symptoms.

Puma Shrugs off an 'Expected' Phase II Failure for Its Breast Cancer Drug

The gist: A new breast cancer drug called neratinib works just as well as Herceptin for some HER2-positive patients. It may also reduce the chances of metastases in the central nervous system; for example, in the brain. Researchers recently tested neratinib in volunteer patients in a clinical trial. They compared it to the drug Herceptin, which is already used by many breast cancer patients. In the trial, neratinib was tested in combination with the chemotherapy drug paclitaxel in people with HER2-positive breast cancer. People who took the neratinib combination had similar survival rates as people who took Herceptin. They had a 52.6% reduction in central nervous system metastases.

“Puma Biotechnology’s ($PBYI) closely watched neratinib failed to beat out the blockbuster Herceptin in a mid-stage breast cancer trial, a miss the company said was no surprise as it touted success on a secondary goal.

“The company recruited 479 patients with HER2- positive breast cancer, testing whether a combination of neratinib and paclitaxel could better prolong progression-free survival (PFS) than a cocktail of Roche’s ($RHHBY) Herceptin and paclitaxel. In the end, median PFS for Puma’s drug came in at 16.6 months, while Herceptin clocked 16.7. And neratinib fared no better on its secondary endpoint, charting a 74.8% overall response rate compared to Herceptin’s 75.1%.

“But Puma is ‘very pleased with the results,’ CEO Alan Auerbach said in a statement, pointing to the secondary endpoint in which neratinib succeeded. The drug contributed to a 52.6% reduction in the incidence of central nervous system metastases–for instance cancer spreading to the brain–compared to the Herceptin arm, a statistically significant result that Puma believes could help differentiate neratinib on the market for breast cancer therapies.

” ‘As expected, there was no statistically significant difference in progression-free survival and objective response rate for the paclitaxel plus neratinib arm compared to the paclitaxel plus trastuzumab arm,’ Auerbach said. ‘However … while the development of other HER2-targeted drugs has produced a clinically meaningful benefit to patients with HER2 positive breast cancer, these drugs have had little impact on CNS metastases. As a result, we believe that there remains an unmet clinical need for reducing the incidence of CNS metastases, and the results of the NEfERTT study demonstrate that we may be able to provide this type of improvement with neratinib. ‘ “

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.


“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.”