Alectinib demonstrated superior efficacy and a safety profile that compared favorably with crizotinib in treatment-naïve ALK+ non-small-cell lung cancer (NSCLC) in the phase III ALEX study. We present patient-reported outcomes (PROs) from ALEX to assess disease burden, treatment-related symptom tolerability, and health-related quality of life (HRQoL) with alectinib versus crizotinib.

Wilms tumor is one of the most common pediatric solid tumors. The pair-like homeobox 2b (PHOX2B) gene is an important transcription factor that regulates cellular proliferation and differentiation in early life. The association between PHOX2B single nucleotide polymorphisms (SNPs) and Wilms tumor risk has not been investigated. Therefore, we conducted a case-control study involving 145 Wilms tumor patients and 531 controls to explore the association between the PHOX2B rs28647582 T>C polymorphism and Wilms tumor susceptibility. The association between the PHOX2B rs28647582 T>C polymorphism and Wilms tumor susceptibility was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Our results indicated that PHOX2B rs28647582 T>C polymorphism did not significantly alter Wilms tumor susceptibility. However, in the stratified analysis, we found that TC/CC genotypes significantly increased Wilms tumor risk among children older than 18 months (adjusted OR = 1.77, 95% CI = 1.07-2.95, P=0.027) and those with clinical stages III+IV (adjusted OR = 1.75, 95% CI = 1.09-2.82, P=0.022), when compared with those with TT genotype. Our study suggested that PHOX2B rs28647582 T>C was weakly associated with Wilms tumor susceptibility. Our conclusions need further validation with a larger sample size.

Recently, mRNA-expression signature enriched in LSCs was used to create a 17-gene leukemic stem cell (LSC17) score predictive of prognosis in adult AML. By fitting a Cox-LASSO regression model to the clinical outcome and gene-expression levels of LSC enriched genes in 163 pediatric participants of the AML02 multi-center clinical trial (NCT00136084), we developed a six-gene LSC score of prognostic value in pediatric AML (pLSC6). In the AML02 cohort, the 5-year event-free survival (EFS) of patients within low-pLSC6 group (n = 97) was 78.3 (95% CI = 70.5-86.9%) as compared with 34.5(95% CI = 24.7-48.2 %) in patients within high-pLSC6 group (n = 66 subjects), p < 0.00001. pLSC6 remained significantly associated with EFS and overall survival (OS) after adjusting for induction 1-MRD status, risk-group, FLT3-status, WBC-count at diagnosis and age. pLSC6 formula developed in the AML02 cohort was validated in the pediatric AML-TARGET project data (n = 205), confirming its prognostic value in both single-predictor and multiple-predictor Cox regression models. In both cohorts, pLSC6 predicted outcome of transplant patients, suggesting it as a useful criterion for transplant referrals. Our results suggest that pLSC6 score holds promise in redefining initial risk-stratification and identifying poor risk AML thereby providing guidance for developing novel treatment strategies.

Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis).

The hepatocyte growth factor receptor mesenchymal-epithelial transition (MET) is reported to be a negative prognostic marker in EGFR-mutant NSCLC and involved in resistance to EGFR inhibitors. Emibetuzumab, a humanized immunoglobulin G4 monoclonal bivalent MET antibody, blocks ligand-dependent and ligand-independent hepatocyte growth factor/MET signaling. This phase 2 study compared erlotinib with and without emibetuzumab in first-line treatment of EGFR-mutant metastatic NSCLC.

This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.

Clinical studies have shown that a combination of a tyrosine kinase inhibitor (TKI) and pemetrexed overcame acquired resistance to epidermal growth factor receptor (EGFR) TKI in NSCLC. Previously, pemetrexed+gefintib (P+G) had improved progression-free survival (PFS) compared with gefitinib. We present OS, updated PFS, biomarker analysis, and safety of P+G versus gefitinib.

EGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).

Dual blockade of the EGFR and VEGF pathways in EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) is supported by preclinical and clinical data, yet the approach is not widely implemented. RELAY assessed erlotinib, an EGFR tyrosine kinase inhibitor (TKI) standard of care, plus ramucirumab, a human IgG1 VEGFR2 antagonist, or placebo in patients with untreated EGFR-mutated metastatic NSCLC.

Fludarabine, cyclophosphamide, and rituximab (FCR) has become a gold-standard chemoimmunotherapy regimen for patients with chronic lymphocytic leukaemia. However, the question remains of how to treat treatment-naive patients with IGHV-unmutated chronic lymphocytic leukaemia. We therefore aimed to develop and validate a gene expression signature to identify which of these patients are likely to achieve durable remissions with FCR chemoimmunotherapy.

Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors.

Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC).

A high 21-gene recurrence score (RS) by breast cancer assay is prognostic for distant recurrence of early breast cancer after local therapy and endocrine therapy alone, and for chemotherapy benefit.

Patients with metastatic colorectal cancer with the BRAF V600E mutation have a poor prognosis, with a median overall survival of 4 to 6 months after failure of initial therapy. Inhibition of BRAF alone has limited activity because of pathway reactivation through epidermal growth factor receptor signaling.

Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma.

Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here.

STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.

The surface receptor MET is highly expressed on primary uveal melanoma; MET inhibitors demonstrated early clinical signals of efficacy in slowing uveal melanoma growth. The primary objective of our study was to compare the progression-free survival rate at 4 months (PFS4) of patients with uveal melanoma treated with cabozantinib or chemotherapy.

Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data.