Individuals with pulmonary nodules detected through lung cancer screening or incidentally often require lung biopsy sampling to differentiate between malignant and benign lesions. Navigational bronchoscopy and CT-guided transthoracic biopsy are both widely used for this purpose, although the comparative performance of these two approaches has been uncertain. Now data from the randomized VERITAS trial

In pivotal trials testing daratumumab in patients with transplant-ineligible newly diagnosed multiple myeloma, inadequate crossover provisions have not only compromised the interpretation of survival data but also left fundamental questions about optimal treatment sequencing unanswered. Herein, we address the ethical implications of trial designs that fail to guarantee access to effective post-progression

More than half of patients with relapsed and/or refractory B cell lymphomas who receive CD19-targeted chimeric antigen receptor (CAR) T cells do not have long-term remission. Furthermore, limited evidence is available on the effectiveness of subsequent treatment options for these patients, the majority of whom have CD19+ disease at relapse. Now, data from a phase I trial demonstrate that the autologous

ERBB2 (commonly known as HER2) is mutated in 2–4% of non-small-cell lung cancers (NSCLCs). The HER2-targeted antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improves both progression-free survival (PFS) and overall survival in patients with advanced-stage NSCLC harbouring these alterations. However, T-DXd comes with a considerable risk of interstitial lung disease (ILD; including fatal

The covalent KRAS-G12C inhibitors adagrasib and sotorasib are approved for patients with previously treated KRASG12C-mutant non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC); however, the efficacy of these agents is limited, in large part, by suboptimal target engagement. Now, data from an ongoing single-arm phase I/II trial indicate that D3S-001 (also known as elisrasib), a next-generation

Patients with resectable mismatch repair-deficient (dMMR) rectal cancer receiving extended neoadjuvant therapy with the anti-PD-1 antibody dostarlimab have previously been shown to have a 100% clinical complete response (cCR) rate. Now, an update from this trial confirms this excellent response rate and provides data on the durability of many of these responses, as well as on the efficacy of this approach

The HARMONi-2 trial demonstrated a significant improvement in progression-free survival with ivonescimab, a bispecific PD-1×VEGF antibody, versus pembrolizumab in patients with PD-L1-positive advanced-stage non-small-cell lung cancer. Ivonescimab might enhance antitumour immunity by normalizing the tumour vasculature and reversing immunosuppression. Although promising, global applicability of ivonescimab

The HIF2α inhibitor belzutifan has shown promising activity in patients with tumours arising in the context of Von Hippel–Lindau disease (VHL), an autosomal-dominant cancer predisposition syndrome arising from the deletion or inactivation of VHL. Now, long-term follow-up data from the phase II LITESPARK-004 trial demonstrate the durable activity of this agent as monotherapy in this population. A total

Patients with progression of metastatic triple-negative breast cancer (mTNBC) following first-line treatment have a dismal prognosis. The TROP2-directed antibody–drug conjugate (ADC) sacituzumab govitecan improves outcomes in this setting. New data from the phase III OptiTROP-Breast01 trial support sacituzumab tirumotecan (sac-TMT), a different anti-TROP2 ADC with a linker designed for improved bioactivity

In 2024, the US FDA approved several new agents for the treatment of patients with cancer, including small-molecule inhibitors, immune-checkpoint inhibitors, bispecific antibodies, antibody–drug conjugates and cell and gene therapy products. Areas of regulatory focus included the accelerated approval programme and diligent completion of post-marketing trials, convening of Oncologic Drugs Advisory Committee

Advanced-stage hepatocellular carcinoma is currently treated with various anti-PD-(L)1 antibody-containing regimens. Now, a triplet combining the anti-TIGIT antibody tiragolumab with one of these regimens has demonstrated promising efficacy in a phase Ib/II trial, although these data will need to be confirmed. This study highlights the value of umbrella trials while also raising questions regarding

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Most patients have considerable tumour shrinkage after IC, yet the radiotherapy target volume is calculated on the basis of the dimensions of the pretreatment tumour, which can result in debilitating toxicities owing to irradiation of

Most patients undergoing surgery for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer will require chemotherapy; however, the optimum approach, including the most effective regimen and whether perioperative chemotherapy is more effective than an adjuvant-only approach, remains uncertain. Now, 5-year follow-up data from the phase III RESOLVE trial provide evidence supporting the

In a recently reported study, a novel engineered oncolytic Newcastle disease virus encoding porcine α1,3-galactosyltransferase was evaluated in monkeys with CRISPR-induced primary hepatocellular carcinoma and in a phase I clinical trial. The virus induced hyperacute tumour rejection and an objective response rate of 35% in 20 evaluable patients. This approach highlights the promises and challenges

The thought-provoking SONIA trial showed that patients with hormone receptor-positive, HER2-negative advanced-stage breast cancer receiving deferred (second-line) versus first-line cyclin dependent-kinase (CDK) 4/6 inhibitors have noninferior progression-free survival after second-line treatment; such an approach also results in substantial cost savings. Herein, we discuss some important limitations

Chimeric proteins resulting from fusions involving NRG1, which encodes a growth factor from the EGF family, promote HER2–HER3 heterodimerization and subsequent oncogenic activation of cell proliferation. These fusions occur in <1% of solid tumours including non-small-cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PDAC). Now, data from the phase II eNRGy trial demonstrate that the HER2 × HER3

Most women with newly diagnosed breast cancer remain alive and recurrence-free for many years after complete surgical resection. Thus, whether all these women require annual follow-up mammography remains uncertain. Now, data from the phase III Mammo-50 trial demonstrate that most women can safely undergo follow-up mammography at 2-yearly or 3-yearly intervals. A total of 5,235 women with previous invasive

Recent data from the FELIX trial evaluating obecabtagene autoleucel in patients with relapsed and/or refractory B acute lymphoblastic leukaemia (R/R B-ALL) suggest that this novel intermediate-affinity CD19-directed chimeric antigen receptor (CAR) T cell therapy is associated with a reduced incidence of severe immune-mediated toxicities compared with other commercially available CAR T cell products

DeepGEM, an artificial intelligence (AI)-based model, accurately predicts the presence of key genomic alterations in histological slides prepared from samples obtained from patients with lung cancer. This approach provides a cost-effective alternative to genomic testing, generates spatial mutation maps and might support personalized treatment strategies. Validated in diverse datasets, DeepGEM highlights

Patients with HER2-negative advanced-stage gastric or gastro-oesophageal junction (G/GEJ) adenocarcinomas typically receive chemotherapy with or without an anti-PD-1 antibody as first-line treatment. Now, data from the phase III COMPASSION-15 trial show that combination of the PD-1 × CTLA4 bispecific antibody cadonilimab plus chemotherapy is also efficacious in this setting. In this trial, conduced

Patients with resectable mid–low rectal cancers often undergo total mesorectal excision (TME) surgery. Over the past decade, considerable research interest has been focused on minimally invasive TME procedures that might offer improved perioperative outcomes and preservation of sphincter function, including laparoscopic and transanal approaches. Despite some evidence of an increased risk of local recurrence

The BCMA-targeted chimeric antigen receptor (CAR) T cell therapy ciltacabtagene autoleucel (cilta-cel) has demonstrated exceptional efficacy in studies conducted worldwide, which has resulted in regulatory approvals in >40 countries. Herein, we examine the regulatory pathways that led to its approval in different regions, focus on challenges in clinical development and regulatory submission, and provide

Two multimodal treatment strategies, perioperative chemotherapy and preoperative chemoradiotherapy, have been shown to improve overall survival (OS) compared to surgery alone in patients with locally advanced oesophageal adenocarcinoma (EAC); however, the optimal approach has been unclear. Newly published results from the phase III ESOPEC trial demonstrate the superiority of the perioperative strategy

Surgical resection is the standard of care for patients with colorectal liver metastases. Thermal ablation has emerged as an alternative management approach for small lesions (≤3 cm diameter), although how it compares with surgery is unclear because most of the available evidence is from meta-analyses of retrospective studies. Now, results from the phase III COLLISION trial demonstrate that thermal

Transarterial chemoembolization (TACE) is the standard-of-care treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) who are not candidates for resection, ablation or transplantation, although disease recurrence is common. Now, early data from two phase III trials demonstrate that the addition of both an immune-checkpoint inhibitor (ICI) and an anti-angiogenic agent to TACE

Recent results from the phase III AQUILA trial demonstrate the benefit of fixed-duration monotherapy with daratumumab over observation in patients with high-risk smouldering multiple myeloma, which changes the early interception treatment landscape. Herein, we discuss how future studies could build on this success and pave the way to eradicating multiple myeloma before it starts.

Haematopoietic stem cell transplantation (HSCT) and CD19-targeted chimeric antigen receptor (CAR) T cells are potentially curative therapies for relapsed and/or refractory diffuse large B cell lymphoma (R/R DLBCL); however, many patients are unable to receive or have further relapse following these treatments. New data from the phase III ECHELON-3 trial demonstrate the promise of a novel combination

Axillary nodal status provides important information on the prognosis of women with invasive breast cancer. However, the required sentinel lymph node biopsy sampling procedure and the associated risks of surgical complications have raised questions regarding the necessity of this procedure in women undergoing breast-conserving surgery for early stage disease. Now, data from INSEMA, a prospective, randomized

Various endocrine therapies and CDK4/6 inhibitors have improved the treatment of ER+HER2−breast cancer, although resistance remains common and often involves ESR1 (encoding ERα) mutations. Now, data from the phase III EMBER-3 trial demonstrate that the next-generation, brain-penetrant, oral selective ER degrader imlunestrant delays disease progression in previously treated patients with ESR1 mutations

Sequencing of plasma cell-free DNA (cfDNA) is commonly performed during pregnancy to screen for fetal aneuploidy. Now, data from the ongoing prospective IDENTIFY study demonstrate that this strategy also enables prompt detection of occult maternal cancers. IDENTIFY is enrolling individuals with unusual or nonreportable cfDNA fetal aneuploidy-screening results but without perceived signs or symptoms

Despite considerable progress, B-cell acute lymphoblastic leukaemia (B-ALL) remains a major cause of cancer-related death in children. Now, data from the phase III AALL1731 trial demonstrate that adding the CD19 × CD3 bispecific T cell engager blinatumomab to chemotherapy significantly improves the outcomes of patients with standard-risk B-ALL with an average or high risk of disease relapse. In this

The combination of the anti-PD-1 antibody nivolumab plus the anti-CTLA4 antibody ipilimumab showed promising efficacy outcomes as first-line therapy in 45 patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) as part of the single-arm, phase II CheckMate 142 trial. Now, data from the phase III CheckMate 8HW trial confirm the efficacy of this

As one of the first studies testing perioperative anti-PD-(L)1 antibodies in resectable non-small-cell lung cancer (NSCLC), NADIM now confirms, in its final report, impressive 5-year clinical outcomes and that a pCR following neoadjuvant therapy translates into improved long-term survival. These data support the development of novel, personalized treatments for locally advanced resectable NSCLC.