Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer.

Purpose: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.

Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC.

Objectives: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure.

Oncogene-Driven Non-Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations.

Unlabelled: Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes" (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients.

Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay.

Real world efficacy of osimertinib in second line/beyond in patients with metastatic EGFR+ non-small cell lung cancer and role of paired tumour-plasma T790M testing at tyrosine kinase inhibitor resistance.

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/subsequent line after resistance to first- and second-generation (1/2G) EGFR-TKI.

Methods: We reviewed electronic records of 202 patients who received osimertinib from July 2015 to January 2019 in the second/subsequent line after progression on prior EGFR-TKI.

Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma.

Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks.

PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer.

Aim: To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC.

Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method.

A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC.

Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression.

Clinical and Genomic Features of Exon 20 Insertion Mutations and Characterization of Expression by Immunohistochemistry in East Asian Non-Small-Cell Lung Cancer.

Purpose: -altered non-small-cell lung cancer (NSCLC) represents a diverse subgroup, including mutations, amplifications, and overexpression. However, exon 20 insertion mutations are emerging as a distinct molecular subtype with expanding therapeutic options. We describe the molecular epidemiology and genomic features of -altered NSCLC in an Asian tertiary cancer center.

Association of Clinicopathologic and Molecular Tumor Features With Recurrence in Resected Early-Stage Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer.

Importance: The recently published ADAURA study has posed a significant dilemma for clinicians in selecting patients for adjuvant osimertinib. Risk factors for recurrence in early-stage epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) also remain undefined.

Objective: To determine clinicopathologic characteristics and recurrence patterns of resected early-stage EGFR-positive NSCLC, using wildtype EGFR as a comparator cohort, and identify features associated with recurrence.

Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer.

Introduction: Circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together.

Methods: Concurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method DropCell platform.

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in -negative resistance.

Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M) and -negative (T790M) disease.

Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M tumors, orthogonally validated using multiplex IHC.

Phase II study of nimotuzumab (TheraCim-hR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma.

Background: The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated in a phase II study.

Methods: Patients with stage III/IV HNSCC received 3-weekly cisplatin 100 mg/m for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression-free survival (PFS).

An Assessment of Health Information Resource Center and Supportive Program Needs.

Objective: No practical method or assessment tool for identifying patients' and their families' health information resource needs in a resource center exists. We sought to assess the health information and resource preferences of patients and their families to guide the planning of a health information resource center (HIRC).

Methods: A needs assessment was conducted using convenience sample of patients and families drawn from the National Cancer Centre in Singapore.

Determining the Concerns of Breast Cancer Survivors to Inform Practice.

Objective: Breast cancer is the most common cancer in women across all ethnicities, accounting for almost one in three incident cancers in female, and the leading cause of mortality in Singapore. Literature reveals that survivors of breast cancer have many concerns, and these concerns can linger on for decades. The primary aim of this secondary analysis was to establish the concerns of breast cancer survivors and use the data to inform practice.

Radium-223 in Asian patients with castration-resistant prostate cancer with symptomatic bone metastases: A single-arm phase 3 study.

Aim: Radium-223, a targeted alpha therapy, is approved widely for the treatment of patients with metastatic castrate-resistant prostate cancer, based on a pivotal phase 3 study in predominantly white patients. We investigated the efficacy and safety of radium-223 in Asian patients with castrate-resistant prostate cancer and metastatic bone disease.

Methods: This multicenter, prospective, single-arm, open-label phase 3 trial evaluated the efficacy and safety of the standard radium-223 regimen (55 kBq/kg every 4 weeks for six cycles) in patients from Asian countries.

Immune checkpoint inhibitor-associated myositis and myasthenia gravis overlap: Understanding the diversity in a case series.

Immune checkpoint inhibitors (ICI) have improved survival across tumor types however they cause immune-related toxicities through removal of the inhibition of auto-reactive T cells. In this case review, we present 4 patients with metastatic cancer who developed de-novo neuromuscular side effects of myositis with overlapping seropositive myasthenia gravis after ICI treatment. Declaration: This study was performed in accordance to the ethical standards set by the SingHealth Institutional Review Board, with consent taken from living patients and waiver of consent from deceased patients (CIRB Ref 2019/2485).

Molecular Characterization and Clinical Outcomes in RET-Rearranged NSCLC.

Introduction: RET rearrangements are an emerging targetable oncogenic fusion driver in NSCLC. However, the natural history of disease and activity of different classes of systemic therapy remain to be defined. Furthermore, molecular testing for RET is not yet routine, and the optimal method of testing is unclear.

Caregivers of cancer patients: what are their information-seeking behaviours and resource preferences?

Cancer impacts not only the patient but also the family members who share the distressing trajectory of the patient. The literature indicates that caregivers have many unmet information needs while providing care and support to the cancer patients, and caregivers have to resort to seeking information to supplement their information needs. This study aims to establish the prevalence of health-information-seeking behaviours among caregivers of cancer patients as a means of ascertaining if their information needs have been met and their information source and resource preference.

Cancer Survivors: What Are Their Information Seeking Behaviours?

This study aims to examine the information seeking behaviours and experiences of cancer survivors at various stages of the cancer survivorship trajectory in Singapore. Data was collected via a self-administered questionnaire from survivors diagnosed with the top 6 cancers in Singapore seen at the National Cancer Centre Singapore (NCCS). Cancer survivorship stages were categorized as newly diagnosed and on treatment (NT), completed treatment or cancer-free ≥ 5 years (CT) and had recurrence or second cancer (RS).

Utility of incorporating next-generation sequencing (NGS) in an Asian non-small cell lung cancer (NSCLC) population: Incremental yield of actionable alterations and cost-effectiveness analysis.

Objectives: There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients.

Association of clinical factors with survival outcomes in laryngeal squamous cell carcinoma (LSCC).

Aim: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population.

Methods: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed.

Real-world outcome with abiraterone acetate plus prednisone in Asian men with metastatic castrate-resistant prostate cancer: The Singapore experience.

Introduction: Several small studies have reviewed the efficacy of abiraterone acetate plus prednisolone (AAP) in clinical practice outside a trial setting. We report the largest cohort study of clinical outcomes in metastatic castrate-resistant prostate cancer (mCRPC) patients treated with AAP in a multicenter multiracial clinical setting.

Methods: A retrospective analysis on mCRPC patients treated at four tertiary hospitals in Singapore from 2012 to 2017 was conducted.

Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Abiraterone acetate plus prednisone or prednisolone improves progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. Radium-223 improves overall survival and delays the onset of symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases. We assessed concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 in such patients.