publication date: Mar. 20, 2020

Clinical Roundup

Pembrolizumab shows promise for some advanced, hard-to-treat rare cancers

A study conducted by researchers at MD Anderson Cancer Center demonstrated acceptable toxicity and anti-tumor activity in patients with four types of advanced, hard-to-treat rare cancers. Study findings were published in the March 17 online issue of the Journal for ImmunoTherapy of Cancer.

The open-label, phase II study followed 127 patients who had advanced rare cancers: squamous cell carcinoma of the skin, carcinoma of unknown primary, adrenocortical carcinoma, and paraganglioma-pheochromocytoma. All patients had tumors that had progressed on standard therapies.

The primary objective of the study was to find the proportion of patients who were alive and progression-free at 27 weeks on treatment with pembrolizumab. The median non-progression rate at that time was 28% for 127 patients with advanced rare cancers. Complete response, partial response or stable disease after four months was observed in 38% of the patients. Non-progression rates for each cancer group were: 36% for cSCC, 33% for CUP, 31% for ACC, and 43% for paraganglioma-pheochromocytoma. Treatment-related adverse events occurred in 52% of patients, with the most common side effects being fatigue and rash, with six deaths reported that were unrelated to treatment.

“Our findings that pembrolizumab has a favorable toxicity profile and anti-tumor activity in patients with these rare cancers supports further evaluation in these populations,” Aung Naing, associate professor of Investigational Cancer Therapeutics, said in a statement. “Finding solutions for treatment is vital given that patients with advanced rare cancers have poor prognosis and few treatment options.”

CUP is a type of cancer in which the primary cancer site is not always known, but has spread to other areas within the body, while ACC occurs when malignant cells form in the outer layer of the adrenal glands.

Paraganglioma-pheochromocytoma are tumors formed in nerve-like cells near the adrenal glands and near blood vessels or nerves in the head, neck, chest, abdomen, and pelvis.


Study suggests link between BMI, nutritional markers, and chemotherapy toxicity in older adults with tumors

A combination of body mass index and levels of albumin, a protein made by the liver, can predict how well older adults with cancer will be able to tolerate the side effects of chemotherapy, according to a study led by a researcher at Fox Chase Cancer Center.

The study was published in Cancer.

“Oncologists should carefully consider these factors as part of a comprehensive GA [geriatric assessment] before recommended chemotherapy for older adults with cancer,” the authors wrote of their findings, which they believe are the first to document a protective effect of high BMI in this population.

The study, led by Efrat Dotan, an associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, used data on 750 patients ranging from 65 to 94 years of age who were treated with chemotherapy. More than half the patients (58.6%) were receiving therapy for metastatic disease. The overarching goal of this large study was to identify the most important factors that affect older adults who are treated with chemotherapy for advanced cancer.

In this report, Dotan and colleagues evaluated the association between chemotherapy toxicity and nutritional factors, including pretreatment BMI, unintentional weight loss in the prior six months, and albumin levels among older adults with solid tumors.

The results showed that among older adults with advanced cancer, higher BMIs and normal albumin levels were associated with a lower risk of grade 3 or higher chemotherapy toxicity, which is graded on a scale of one to five. A score of one indicates minor toxicity and five indicates patient death, Dotan said.

“The main conclusion from this study is that monitoring patients’ BMI is important and can predict for outcomes among older cancer patients who are undergoing anti-cancer therapy,” she said.

“In this study, patients with BMI that was greater than 30 saw the highest benefit in terms of chemotherapy tolerance,” Dotan said. These findings bring into question the appropriate BMI recommendations for older adults, as BMI greater than 30 is categorized as obesity and considered unhealthy by the Centers for Disease Control and Prevention.


Study: Melanoma is killing fewest Americans

Advances in treatment have led to the largest yearly declines in deaths due to melanoma ever recorded for this skin cancer, results of a study suggest.

Led by researchers at NYU Grossman School of Medicine, its Perlmutter Cancer Center, and Harvard University, the study showed that death rates among white Americans—the group that accounts for almost all cases—climbed 7.5% between 1986 and 2013, but then dropped by nearly 18% over the next three years.

The authors say the size of the declines outstrip comparable decreases in cancers of the prostate, breast, and lung. They also note that the unrivaled drop in melanoma deaths coincided with the introduction of 10 treatments. These treatments either harness the body’s immune system to fight the disease or directly target melanoma cells that have a specific gene mutation.

“Our findings show how quickly patients and physicians accepted these new drugs because they profoundly reduce deaths from melanoma,” co-senior study author David Polsky, said in a statement.

The report, published American Journal of Public Health, is the first to highlight the role of these new drugs in helping Americans survive melanoma, says Polsky, who is also a professor in the Department of Pathology at NYU Langone.

The newer therapies, which came into use in the last decade, are far more effective and less toxic than standard chemotherapy, but are much more expensive, the investigators say. The drugs fall into two broad categories: those that target the BRAF gene, which is mutated in a little less than half of melanoma patients; and immune checkpoint inhibitors, which prevent melanoma tumors from tricking the immune system into ignoring the cancer.

For the study, researchers analyzed new cases and deaths from melanoma collected by NCI and CDC. These numbers spanned from 1986 to 2016 and involved nearly a million Americans. Polsky notes that the steep drop in deaths cannot be readily explained by better detection methods, because death rates did not drop steadily over time, but sharply. In addition, many health care groups have been pushing for early detection exams since the 1980s, so the timing of these declines matches up better with the introduction of the new therapies.

Copyright (c) 2020 The Cancer Letter Inc.