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PADA-1 is the first trial to demonstrate benefit from a treatment-switching strategy guided by active monitoring of ESR1 mutations in plasma circulating tumour DNA (ctDNA) from patients with breast cancer. The results of this trial raise important questions about the specific treatment approach tested, and the feasibility of trials incorporating longitudinal ctDNA analyses to anticipate resistance and guide treatment.
The first phase III trial to test perioperative immune-checkpoint inhibitor therapy for high-risk renal cell carcinoma yielded highly promising results, leading to regulatory approvals of adjuvant pembrolizumab. However, subsequent phase III trials, including the IMmotion010 trial of adjuvant atezolizumab, did not demonstrate similar benefits. Although molecular biomarkers are urgently needed to better delineate responder subgroups, the unique design of each trial might partially explain some of the patterns identified.
CAR T cell therapy has altered the natural history of relapsed and/or refractory diffuse large B cell lymphoma (DLBCL). However, the availability of multiple products has created provider uncertainty regarding treatment selection and the need to balance toxicity and efficacy. In a retrospective analysis, the authors suggest that axicabtagene ciloleucel might be superior to tisagenlecleucel. However, several questions remain unresolved.
A high tumour mutational burden (≥10 mutations per megabase) is a companion biomarker in the histology-agnostic approval of pembrolizumab for treatment-refractory advanced-stage solid tumours, and continues to be an exploratory predictive biomarker for immune-checkpoint inhibitors in non-small-cell lung cancer. Herein, we discuss recent results from the first phase III trial evaluating blood-based tumour mutational burden in patients with treatment-naive advanced-stage non-small-cell lung cancer.
Clinical trials of neoadjuvant therapy for melanoma have expanded rapidly over the past several years. Preliminary data demonstrate the prognostic value of pathological response, which might have clinical implications for refining the roles of surgery and adjuvant therapy. These clinical questions are under active investigation across many ongoing clinical trials.
The development of covalent, allele-specific inhibitors of KRASG12C represents a major breakthrough in precision oncology. Herein we discuss recent data from the phase II KRYSTAL-1 trial of adagrasib in KRASG12C-mutated non-small-cell lung cancer (NSCLC). This trial showed responses in a subset of patients, including among those with brain metastases, and offers exploratory insights into potential biomarkers of response.
Data on a new treatment approach utilizing bispecific monoclonal antibodies targetting B-cell maturation antigen (BCMA) were recently published, yielding very encouraging results in the setting of relapsed and/or refractory multiple myeloma (RRMM). How to safely and effectively deliver this treatment to patients and where it fits in the RRMM treatment paradigm are important questions for the future.
Tracking circulating tumour DNA (ctDNA) after surgery holds promise for patient management and therapeutic intervention in non-small-cell lung cancer (NSCLC). A study published by Zhang and colleagues tracks ctDNA from 261 patients with stages I–III NSCLC and suggests that the likelihood of disease relapse decreases for high-risk stage II/III patients after 18 months without ctDNA detection.
A recent study not only confirms mounting evidence that technology-facilitated symptom monitoring improves care and should be considered for all patients with cancer, but also suggests that patient navigators can help to deliver such interventions. Herein we discuss how such an approach can minimize disparities and maximize access to culturally appropriate patient-centred care.
Immune-checkpoint inhibitors have revolutionized the treatment of patients with non-small-cell lung cancer (NSCLC). Recently, indications for immune-checkpoint inhibitors have expanded from advanced-stage NSCLC to adjuvant, and now neoadjuvant, therapy for resectable NSCLC, with three cycles of preoperative chemoimmunotherapy achieving superior pathological complete response rates and event-free survival compared with chemotherapy alone in the phase III CheckMate 816 trial.
Two recent large-cohort studies reinforce the potential predictive capability of gut microbiota for immune-checkpoint inhibitor response and toxicities in patients with melanoma. However, additional investigations are required to understand the mechanistic underpinnings of this complex multifaceted relationship, and how it can be exploited for personalized cancer care.
To achieve health equity, we advocate for the overrepresentation of particular racial and ethnic minority groups so that analyses of group-specific treatment effects can be optimally powered. A paradigm shift is needed across multiple stakeholders, as well as in the engagement of community programmes, the role of investigators from racial and ethnic minority backgrounds and clinical trial regulations.
Over the past decade, iterative improvements to models predicting breast cancer risk have primarily come from new information about genetic risk factors and improvements to mammogram-based risk scores. Epigenetic risk factors offer some potential to further improve risk stratification. However, the recently developed DNA methylation score (the WID-BC index) is not yet convincing for predicting breast cancer risk.
Non-small-cell lung cancer (NSCLC) is a growing public-health threat, with one of the highest mortality risks among non-communicable diseases. Now, researchers have developed a diagnostic tool for NSCLC by mass spectrometry of a targeted panel of lipids. Herein, we discuss key aspects that could facilitate the clinical implementation of this and similar tools in other fields of application.
Patients with pancreatic ductal adenocarcinoma (PDAC) usually have a dismal prognosis, and even after curative resection most patients will have disease relapse and ultimately die. Nonetheless, adjuvant chemotherapy has considerably improved the outcomes of patients who are able to undergo surgery. The PREOPANC trial provides some evidence supporting the use of neoadjuvant therapy for patients with borderline resectable PDACs but not, as claimed, for those with resectable tumours.
Surgical quality remains a priority for patients with cancer, payers and policymakers. Whether the risk-standardized mortality rate (RSMR) is a better metric than surgical volume to inform the regionalization of cancer surgery remains controversial. In particular, RSMR has been criticized on both theoretical and methodological grounds. Novel alternative means that incorporate surgical volume, as well as evidence-based process measures, are needed.
