Background Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively

Background Enasidenib is an oral inhibitor of mutant isocitrate dehydrogenase-2 (IDH2) proteins. We evaluated the safety and activity of enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia ineligible for intensive chemotherapy. Methods This open-label, phase 1b/2 trial was done at 43 clinical sites in 12 countries (the USA, Germany

Background The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin. Methods This multicentre, open-label, randomised, phase

Background No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients. Methods This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial

Background Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are oral targeted agents approved for use in combination with endocrine therapy as first-line or second-line treatment of patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer. We previously reported the pooled analyses of progression-free survival in patients in specific clinicopathological subgroups,

Background In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified

Background In some countries, breast cancer age-standardised mortality rates have decreased by 2–4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised

Background A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against

Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult

Background Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory

Background The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using

Background The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine

Background CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab

Background Both continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax–obinutuzumab are effective for previously untreated chronic lymphocytic leukaemia. We hypothesised that frontline time-limited, minimal residual disease (MRD)-guided triplet therapy with acalabrutinib, venetoclax, and obinutuzumab would induce deep (ie, more patients with undetectable MRD) and durable remissions

Background In the primary analysis of the pivotal JULIET trial of tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, the best overall response rate was 52% and the complete response rate was 40% in 93 evaluable adult patients with relapsed or refractory aggressive B-cell lymphomas. We aimed to do a long-term follow-up analysis of the clinical outcomes and correlative

Background Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods We did a cohort study with data from

Background The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies

Background There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma. Methods RAMES was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial done at 26 hospitals in Italy. Eligible patients

Background A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with

Background The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2–3 years of letrozole in postmenopausal patients with breast cancer who have already received 2–3 years of tamoxifen. Methods This multicentre, open-label

Background Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition to first-line cisplatin–gemcitabine in patients with locally advanced or metastatic biliary

During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials

The 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and

Over the past two decades, targeted therapies have become cornerstone treatments for numerous cancers with oncogene addiction. Unfortunately, their effectiveness reduces over time and most patients who receive targeted therapies relapse within 12 months. The emergence of drug-resistance mechanisms in tumours paved the way for next-generation inhibitors. However, insufficient concentration of targeted

Integration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an