Immunotherapies Could Open the Door for Additional Treatments in Mucosal Melanoma

“Despite limited information on treatment options for mucosal melanoma, Richard Joseph, MD, says immunotherapies could be a rewarding challenge for oncologists to undertake in the field.

“Joseph, a medical oncologist at Mayo Clinic, says one recent study investigating the immunotherapy nivolumab in the treatment of mucosal melanoma resulted in response rates that could possibly warrant further investigation.

” ‘What they found was that the response rates tended to be slightly lower than what we typically see in cutaneous melanoma, but still a relatively good response rate,’ he said.

” ‘This gives us, for the time being, some quality data for when we are treating patients with mucosal melanoma. We can now give our patients some good numbers regarding if we should treat them with immunotherapy. Before, we were treating them with immunotherapy without really knowing the efficacy.’ “


Greater MET/CEP7 Expression May Predict Therapy Response in NSCLC

“Patients with non–small cell lung cancer who had higher MET positivity appeared less likely to harbor other cancer drivers, according to study results.

“Thus, a greater MET/CEP7 ratio — or a comparison of the MET copy number to the number of chromosome 7 centromeres — may predict benefit from treatment with crizotinib (Xalkori, Pfizer) in patients with NSCLC.

“ ‘Generally, there are two ways that the number of copies of the MET gene can be increased: the tumor can make multiple copies of the entire chromosome on which it sits — chromosome 7 — or it can amplify just the MET region,’ Sinead A. Noonan, MD, senior thoracic oncology fellow at University of Colorado School of Medicine, said in a press release. ‘In the first case, MET is unlikely to be the specific driver of the cancer’s biology. But if the MET region is amplified separate from the rest of the chromosome, this should suggest that the MET gene is indeed the area of specific importance to the cancer.’ “


Pembrolizumab Cutaneous Adverse Events May Predict Better Response

“In a single-center retrospective review reported in JAMA Dermatology, Sanlorenzo et al found that cutaneous adverse events in patients receiving the anti–PD-1 agent pembrolizumab (Keytruda), currently approved for treatment of melanoma, may indicate better treatment response.

“The study was a retrospective record review of 83 consecutive patients treated with pembrolizumab in two studies from March 2011 to May 2014 at the University of California, San Francisco, who had received at least one dose of pembrolizumab and had at least one follow-up visit. Among the patients, 66 had melanoma, 15 lung cancer, 1 prostate cancer, and 1 Merkel cell carcinoma. Patients received pembrolizumab regimens of 10 mg/kg every 3 weeks (n = 43), 10 mg/kg every 2 weeks (n = 24), and 2 mg/kg every 3 weeks (n = 16).

“Median follow-up was 15 weeks (range = 2–105 weeks). Overall, 35 patients (42%) developed cutaneous adverse events attributed to pembrolizumab, with the most common being macular papular eruption (29%), pruritus, (12%), and hypopigmentation (8%), with all cases of hypopigmentation occurring in melanoma patients.”


Pembrolizumab Skin Reactions Tied to Better Cancer Survival

“Skin reactions may affect up to 42% of patients treated with pembrolizumab (Keytruda, Merck & Co, Inc) and could indicate better progression-free survival, according to a retrospective review published online July 29 in JAMA Dermatology.

” ‘Cutaneous adverse events are frequent but mild during pembrolizumab treatment. The development of cutaneous adverse events, especially of hypopigmentation, in patients affected by melanoma, could point toward better treatment response,’ commented first author Martine Sanlorenzo, MD, of the University of California, San Francisco.

“Pembrolizumab is an anti–programmed death-1 drug that has shown promise in treating melanoma, non–small cell lung cancer, and renal cell cancer. The drug is a monoclonal antibody that targets the programmed death–1 (PD-1) receptor on T lymphocytes, which functions in immune inactivation. Tumor cells that express the programmed death ligand–1 (PDL-1) take advantage of the PD-1 receptor to evade the immune response.”


Promising Trial of Brigatinib Shows All Next-Gen ALK Inhibitors May Not Be Created Equal

“Phase I/II clinical trial results reported at the American Society for Clinical Oncology (ASCO) Annual Meeting 2015 show promising results for investigational drug brigatinib against ALK+ non-small cell lung cancer (NSCLC), with 58 of 78 ALK+ patients responding to treatment, including 50 of 70 patients who had progressed after previous treatment with crizotinib, the first licensed ALK inhibitor. Progression-free survival (PFS) in patients previously treated with crizotinib was 13.4 months.

” ‘Although still only in an early phase trial, brigatinib is showing an objective response rate in approximately 70 percent of ALK-positive post-crizotinib and it’s showing about a year of progression-free survival. These results are among the best in the field, offering a lot of hope to people with ALK-positive ,’ says D. Ross Camidge, MD, PhD, director of thoracic oncology at the University of Colorado Cancer Center and the trial’s principal investigator.”


‘Immune Checkpoint’ Drugs Show New Promise for Treating Non-Small Cell Lung Cancer


It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…


A Breast Cancer Tumor's Immune Signature Could Predict Response to Neoadjuvant Therapy

“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.

“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”


Gut Bacteria May Be Necessary for Best Response to Cancer Treatment

The human gut has many bacteria and other microscopic creatures that live inside us, but do not harm us, and may indeed contribute to our health. Now two studies suggest that these bacteria are required for a full response to cancer treatment. Mice that were raised in a sterile environment (and thus lacked any gut bacteria), or whose gut bacteria had been destroyed with antibiotics, were implanted with cancer cells. When these mice were treated with immunotherapy or chemotherapy drugs, their tumors shrank less than those of mice with intact gut bacterial populations. These findings raise concerns for cancer patients, who are frequently treated with antibiotics to control infections due to weakened immune systems.


Gut Bacteria May Be Necessary for Best Response to Cancer Treatment

The human gut has many bacteria and other microscopic creatures that live inside us, but do not harm us, and may indeed contribute to our health. Now two studies suggest that these bacteria are required for a full response to cancer treatment. Mice that were raised in a sterile environment (and thus lacked any gut bacteria), or whose gut bacteria had been destroyed with antibiotics, were implanted with cancer cells. When these mice were treated with immunotherapy or chemotherapy drugs, their tumors shrank less than those of mice with intact gut bacterial populations. These findings raise concerns for cancer patients, who are frequently treated with antibiotics to control infections due to weakened immune systems.