“While immunotherapy with programmed death receptor 1 (PD-1) inhibiting antibodies has revolutionized the treatment of non-small cell lung cancer (NSCLC), use of these agents comes at the cost of potential serious immune-related adverse events (irAEs). In melanoma, development of cutaneous irAEs, such as rash and vitiligo, during treatment with PD-1 inhibitors has been shown to be associated with survival benefit, suggesting that early onset of irAEs may predict treatment outcomes. However, in NSCLC, the predictive value of immunotherapy-related toxicity as a clinical marker for efficacy to PD-1 inhibition is unknown. A multi-institution retrospective study investigated the relation between the development of irAEs and efficacy of PD-1 inhibitors in 134 patients with advanced or recurrent NSCLC who received second-line treatment with nivolumab. The primary outcome for this analysis was progression-free survival (PFS) according to the development of irAEs in a 6-week landmark analysis.”
“Anti-programmed cell death (PD)-1 therapy for metastatic melanoma is associated with the development of immune-related cutaneous events, according to research published in the March issue of the Journal of the American Academy of Dermatology.
“Shelley Ji Eun Hwang, M.B.B.S., from the University of Sydney, and colleagues reviewed the clinical and histologic information of 82 patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at one institution from May 2012 to February 2015.”
“Adverse events related to immune activation with ipilimumab (Yervoy, Bristol-Myers Squibb Company) may be higher than clinical trials have previously suggested, according to a study of real-world clinical data from patients treated at Memorial Sloan Kettering Cancer Center, in New York City. The study was published online August 17 in the Journal of Clinical Oncology.
“Ipilimumab was the first of the novel immunotherapies launched for melanoma, and so far it is the only one that is an anticytotoxic T-cell lymphocyte-4 (anti-CTLA-4) antibody. It can cause immune activation and adverse reactions, such as diarrhea, rash, hepatitis, and pituitary inflammation. These reactions are often treated with steroids; severe reactions may require treatment with an anti–tumor necrosis factor alpha (anti-tNFα), such as infliximab (Remicade, Janssen Biotech, Inc).
” ‘Among our small group of physicians highly experienced with ipilimumab, we felt that 35% of the patients required systemic steroids to treat adverse events,’ commented lead author Paul Chapman, MD, a specialist in metastatic melanoma at Memorial Sloan Kettering Cancer Center.”
“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.”
“Clinicians who have been treating patients with melanoma using immunotherapy are warning that autoimmune pneumonitis, sometimes with respiratory distress that necessitates intensive care, is ‘a rare but potentially serious toxic effect’ associated with the new programmed cell death (PD) inhibitors.
“Two such drugs are on the market: nivolumab (Opdivo, Bristol-Myers Squibb) for melanoma and non–small cell lung cancer and pembrolizumab (Keytruda, Merck Sharpe & Dohme) for melanoma. Both list pneumonitis as an adverse event in their product labels.
“The clinicians, with first author Mizuki Nishino, MD, all from Dana Farber/Brigham and Woman’s Hospital in Boston, Massachusetts, report three cases of immune-pneumonitis seen after treatment with nivolumab in a letter published in the July 16 issue of the New England Journal of Medicine.”
Lee, YC, Jin, JK ... Gallick GE, Lin, SH. Molecular Cancer Research. Jan. 21, 2013.
Researchers from the MD Anderson Cancer Center in Houston show that β1 integrin activation occurs in metastatic progression of prostate cancer and is constitutively active in late state prostate cancer cells. The study shows the integrin palys a reole in survival of metastatic prostate cancer cells in circulation. Inhibition of β1 integrin activity by antibody or knockdown results in increased apoptosis.
Grubb, RL, Andriole, GL ... Manyak, MJ, Castro, R. Journal of Urology. Jan. 22, 2013.
Nearly 2,800 men participated in the four-year REDUCE (REduction by DUtasteride of prostate Cancer Events) observational clinical study evaluated prostate cancer risk reduction in men taking dutasteride, a 5-alpha-reductase inhibitor (5ARI) typically used to treat enlarged prostate. Results showed that few new prostate cancers were detected during the two-year follow-up in either treatment group and no deaths were reported. However, the former dutasteride group produced double the number of cancers than the former placebo group (14 vs. 7).
Aryee, MJ, Liu, W ... Bova, GS, Yegnasubramanian, S. Science Translational Medicine. Jan. 23, 2013.
Researchers at Johns Hopkins analyzed 13 metastatic prostate tumors, finding a a consistent epigenetic signature among the samples. The discovery of the stable, epigenetic “marks” that sit on the nuclear DNA of cancer cells and alter gene expression, defies a prevailing belief that the marks vary so much within each individual’s widespread cancers that they have little or no value as targets for therapy or as biomarkers for treatment response and predicting disease severity.
Hassan, S, Karpova, Y ... Datta, SR, Kulik, G. Journal of Clinical Investigation. Jan. 25, 2013.
We know stress is bad for cancer patients in general. Now, a new study shows mouse prostate cancer models under stress (they can smell a predator) had lower responses to cancer drug compared to non-stressed counterparts. A linked commentary suggests drugs such as beta-blockers that affect adrenaline could boost efficacy of anti-cancer treatments.