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).”


Urine Test for PCA3 Helps Patients Avoid Unnecessary Prostate Biopsies

“In a study reported in the Journal of Clinical Oncology, Wei et al found that use of urinary prostate cancer antigen 3 (PCA3) measurement could improve avoidance of repeat prostate biopsy and detection of prostate cancer in biopsy-naive patients.

“This National Cancer Institute study involved 859 men (mean age, 62 years) from 11 centers scheduled for diagnostic prostate biopsy between December 2009 and June 2011.

“PCA3 scores were reported as a ratio of urinary PCA3 mRNA to prostate-specific antigen mRNA. Among men presenting for initial prostate biopsy, PCA score > 60 had a sensitivity of 42%, specificity of 91%, and positive predictive value of 80% (95% confidence interval [CI] = 72%–86%) for detection of any cancer. Among men presenting for repeat biopsy, PCA score < 20 had negative predictive value of 88% (95% CI = 81%–93%), with sensitivity and specificity of 76% and 52% for absence of cancer…

“The investigators concluded: ‘These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (>60) significantly increases the probability that an initial prostate biopsy will identify cancer.’ “


CureVac Completes Patient Recruitment for Phase IIb Clinical Trial of mRNA-based Prostate Cancer Treatment

“CureVac, a German clinical stage biopharmaceutical company, today announced that it has reached the targeted number of patients for its phase IIb clinical trial of the mRNA-based immunotherapy CV9104 in patients with prostate cancer within the anticipated timeline. To date, CureVac has included more than 195 chemotherapy naïve patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC) in eight European countries into the study.”


Network-Based Stratification of Tumor Mutations

“Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence.”


Network-Based Stratification of Tumor Mutations

“Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence.”


Network-Based Stratification of Tumor Mutations

“Many forms of cancer have multiple subtypes with different causes and clinical outcomes. Somatic tumor genome sequences provide a rich new source of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely share the same mutations. Here we introduce network-based stratification (NBS), a method to integrate somatic tumor genomes with gene networks. This approach allows for stratification of cancer into informative subtypes by clustering together patients with mutations in similar network regions. We demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of clinical outcomes such as patient survival, response to therapy or tumor histology. We identify network regions characteristic of each subtype and show how mutation-derived subtypes can be used to train an mRNA expression signature, which provides similar information in the absence of DNA sequence.”


Genetic Ablation of Epidermal EGFR Reveals the Dynamic Origin of Adverse Effects of Anti-EGFR Therapy

“Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients’ plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils.”


New Cancer Vaccine Enters Phase IIb Clinical Trial for Patients with CRPC

CureVac, a German biopharmaceutical company, announced the start of a phase IIb clinical trial of its vaccine, CV9104, for castration-resistant prostate cancer (CRPC). The vaccine works by prompting the body’s own immune system to attack prostate cancer cells. The trial will enroll up to 200 patients across eight European countries who have never received chemotherapy for CRPC. For more information on the clinical trial click here.


CureVac Initiates Phase 2b Clinical Trial of its mRNA-Based Cancer Vaccine in Patients with Castration-Resistant Prostate Cancer

CureVac GmbH, a clinical stage biopharmaceutical company that has pioneered the development of a new class of therapies and vaccines based on messenger RNA (mRNA), today announced that it has initiated a double-blind, randomized Phase 2b clinical trial of its RNActive® cancer vaccine, CV9104, for the treatment of patients with castration-resistant prostate cancer.”