T-VEC/Pembrolizumab Combination Demonstrates Safety in Melanoma

“The combination of the attenuated oncolytic virus talimogene laherparepvec (T-VEC) and the immune checkpoint inhibitor pembrolizumab has passed an early safety evaluation for unresectable melanoma, investigators reported at the 2015 European Cancer Congress (ECC).

“Treatment-related grade 3 adverse events occurred infrequently in a small phase Ib trial of combination therapy with T-VEC and pembrolizumab. No patient discontinued treatment because of adverse events and no treatment-related deaths occurred.

“ ‘T-VEC plus pembrolizumab was well tolerated, and we observed no dose-limiting toxicity,’ said Georgina V. Long, BSc, PhD, MBBS, associate professor at the University of Sydney in Australia. ‘Treatment-related adverse events were mostly grade 1/2. The combination of T-VEC and pembrolizumab is feasible and warrants further investigation.’ “


ASCO: Nivolumab Treatment in Melanoma Patients Has Manageable Safety Profile

“The monoclonal antibody nivolumab has shown promise as a therapeutic agent, particularly by improving the survival rates of melanoma patients. Jeffrey S. Weber, M.D., Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center will be presenting data from a retrospective analysis of the safety of nivolumab in 4 ongoing phase I-III studies in melanoma patients at the 2015 American Society of Clinical Oncology Annual Meeting in Chicago.

“Nivolumab targets a protein called the programmed death-1 (PD-1) receptor. The PD-1 pathway plays an important role in controlling the immune system to prevent inadvertent immune cell activation and autoimmune disease. PD-1 is found on immune cells called T cells, while its ligand PD-L1 is expressed on antigen presenting cells. Binding of PD-L1 to PD-1 inhibits the replication and activity of immune cells and prevents an immune response. Melanoma cells express high levels of PD-L1 to avoid immune detection and improve their survival potential.”


Ipilimumab Demonstrates Long-Term Survival Benefit in Advanced Melanoma

“Some patients with advanced melanoma treated with ipilimumab continued to derive a survival benefit at least 5 years after treatment, according to study results.

“The results showed that, for certain patients, retreatment with ipilimumab (Yervoy, Bristol-Myers Squibb) can re-establish disease control while demonstrating a safety profile comparable to that observed during ipilimumab induction, researchers wrote.

“The analysis included patients treated with ipilimumab in one of six phase 2 clinical trials. In those trials, ipilimumab was administered in doses of 0.3 mg/kg, 3 mg/kg or 10 mg/kg.

“In the current companion study — conducted by Celeste Lebbé, MD, PhD, professor of dermatology at Hôpital Saint-Louis in Paris, and colleagues — patients underwent ipilimumab retreatment, extended maintenance therapy or follow-up for survival only.”


Report Card on Complementary Therapies for Breast Cancer

“Over eighty percent of breast cancer patients in the United States use complementary therapies following a breast cancer diagnosis, but there has been little science-based guidance to inform clinicians and patients about their safety and effectiveness. In newly published guidelines from the Society for Integrative Oncology, researchers at Columbia University’s Mailman School of Public Health and the Herbert Irving Comprehensive Cancer Center with colleagues at MD Anderson Cancer Center, University of Michigan, Memorial Sloan Kettering, and other institutions in the U.S. and Canada, analyzed which integrative treatments appear to be most effective and safe for patients. They evaluated more than 80 different therapies.

“Meditation, yoga, and relaxation with imagery were found to have the strongest evidence supporting their use. They received an “A” grade and are recommended for routine use for anxiety and other mood disorders common to breast cancer patients. The same practices received a “B” grade for reducing stress, depression, and fatigue, but are also endorsed for most breast cancer patients. Acupuncture received a “B” grade for controlling chemotherapy induced nausea and vomiting and can be recommended to most patients. More than 30 interventions, including some natural products and acupuncture for other conditions, had weaker evidence of benefit due to either small study sizes or conflicting study results, and received a “C” grade. Seven other therapies were deemed unlikely to provide any benefit and are not recommended. One therapy was found to be harmful: acetyl-l-carnitine, which is marketed to prevent chemotherapy-related neuropathy, and actually increased risk for the condition.”


Abiraterone Acetate/Prednisone in Metastatic Castration-Resistant Prostate Cancer: Final Analysis of Early-Access Protocol Study

The gist: In 2012, the U.S. Food and Drug Administration (FDA) approved a drug called Zytiga for the treatment of metastatic castration-resistant prostate cancer. It is prescribed along with the drug prednisone. Before the FDA’s approval, the Zytiga/prednisone combination was being tested in patients in a clinical trial. The trial was an “early-access” trial, meaning that it gave patients access to a very promising treatment that had not yet been approved. All patients involved had metastatic castration-resistant prostate cancer that had worsened after chemotherapy. Recently reported results from the trial showed no new safety concerns for the treatment.

“Abiraterone acetate (Zytiga) is approved for use in combination with prednisone in the treatment of metastatic castration-resistant prostate cancer. As reported by Sternberg et al in The Lancet Oncology, results of an open-label, early-access protocol trial initiated prior to approval indicated no new safety signals with abiraterone acetate plus prednisone given after progression on chemotherapy…

“The study, conducted in 23 countries, included 2,314 patients with metastatic castration-resistant prostate cancer progressing after taxane chemotherapy enrolled between November 2010 and September 2013. Patients received abiraterone acetate 1,000 mg/day and prednisone 5 mg twice a day in 28-day cycles until disease progression, development of sustained side effects, or approval and availability of abiraterone acetate in the country of residence…

“The investigators concluded: ‘No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients’ outcomes.’ ”


New Prostate Cancer Treatment Convenient, Less Expensive, but May be Riskier

“A faster and less expensive form of radiotherapy for treating prostate cancer may come at a price, according to a new study by Yale School of Medicine researchers—a higher rate of urinary complications.

“The standard external beam radiation therapy for prostate cancer is called intensity modulated radiation therapy (IMRT). Stereotactic body radiotherapy (SBRT) is a newer treatment that delivers a greater dose of radiation per treatment than IMRT. As a result, patients receiving SBRT can complete an entire course of treatment in one to two weeks, compared to seven to nine weeks for IMRT. There have been few studies comparing the costs of these treatments, and their toxicity.”


‘Real World’ Safety Study of Vemurafenib in BRAF V600–Mutated Metastatic Melanoma Shows Similar Safety Profile as Pivotal Trials

“As reported in The Lancet Oncology by Larkin et al, interim results of a safety study designed to reflect the spectrum of patients encountered in routine practice suggest that vemurafenib (Zelboraf) has a safety profile in patients with BRAF V600–mutated metastatic melanoma similar to that observed in the more select patient population included in registration trials. The study included patients with limited treatment options and sizable proportions with brain metastases, elevated lactate dehydrogenase (LDH), poor performance status, and age ≥ 75 years.”

Editor’s Note: The important takeaway from this story is that the drug vemurafenib can be used safely and effectively in some melanoma patients with poor prognoses, who may not fit the profile of patients typically enrolled in clinical trials to test the drug. To learn more about clinical trials and “targeted therapies” like vemurafenib, visit our Melanoma Basics.


Radiation Therapy Can Treat Suspected Lung Cancer Without Biopsy

Some patients with suspected lung cancer cannot undergo a biopsy due to other illnesses or overall frailty; for others, biopsies are performed, but with inconclusive results. For these patients, the diagnosis of lung cancer often rests on strong evidence from computed tomography (CT) or positron emission tomography (PET) scans. In many of these cases, lung cancer also cannot be treated with surgery. A recent study confirms radiation therapy as a safe and effective method for controlling lung cancer in such patients. Thirty-four patients with unbiopsied lung cancer received stereotaxic body radiation therapy (SBRT). Tumors stopped growing in all patients but 1, shrank in 7 patients, and disappeared entirely in 8 of them. No severe side effects were observed. Another study demonstrated that SBRT, in which focused, high doses of radiation are given over a relatively small number of sessions, is more effective against inoperable non-small cell lung cancer (NSCLC) than traditional, conventionally fractioned radiotherapy (CFR).


Four-Drug Combination Shown to Be Safe and Effective for NSCLC

A combination of the drugs carboplatin (Paraplatin), paclitaxel (Taxol/Abraxane), cetuximab (Erbitux), and bevacizumab (Avastin) has demonstrated effectiveness against non-small cell lung cancer (NSCLC) in a phase II clinical trial. One hundred two patients with advanced non-squamous NSCLC received the four-drug combo as a first-line treatment. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Patients went an average of 7 months without their cancer progressing; the average survival time was 15 months. Four treatment-related deaths occurred, including two due to hemorrhage (heavy bleeding), which can be a rare but serious effect of Avastin treatment. This side effect profile was within the predefined safety margin. A phase III trial further investigating this drug combination for NSCLC is currently enrolling participants.