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  • BCMA-directed chimeric antigen receptor T cell therapies and bispecific T cell engagers are moving to earlier lines of therapy in multiple myeloma. In addition, combination therapy with the BCMA-targeting antibody–drug conjugate belantamab mafodotin at first or subsequent relapse has the potential to improve survival of patients with this disease. This increasing number of therapeutic options makes treatment selection and sequencing increasingly complex.

    • Niels W. C. J. van de Donk
    • Sonja Zweegman
    News & Views
  • The NETTER-2 trial provides the first phase III evidence that 177Lu-dotatate is active as first-line therapy in patients with gastroenteropancreatic neuroendocrine tumours with a Ki-67 proliferative index of 10–55%. This approach is an important addition to the first-line therapeutic armamentarium, although treatment selection based on patient-specific and tumour-specific characteristics remains appropriate.

    • Jonathan Strosberg
    • Mauro Cives
    News & Views
  • De-escalation of treatment for HER2+ breast cancer is a priority, given the increase in cure rates owing in part to improved HER2-targeted therapies. In this regard, the neoadjuvant approach provides the ideal platform to test less-intensive treatment regimens. Here we highlight a study that demonstrated the role of the metabolic response after dual HER2 blockade as a method of selecting patients who are most likely to benefit from chemotherapy-free neoadjuvant therapy.

    • Maria Vittoria Dieci
    • Valentina Guarneri
    News & Views
  • The majority of patients with cancers of unknown primary have unfavourable outcomes when they receive empirical chemotherapy. The shift towards using precision medicine-based treatment strategies involves two options: tissue-agnostic or site-specific approaches. Here, we reflect on how cytology-based deep learning tools can be leveraged in these approaches.

    • Elie Rassy
    • Nicholas Pavlidis
    News & Views
  • The FDA has approved nanoliposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin (NALIRIFOX) for patients with metastatic pancreatic adenocarcinoma on the basis of results from the NAPOLI 3 trial, in which this four-drug regimen improved overall survival relative to a doublet regimen. Here we discuss how, in the context of prior results from the PRODIGE 4 trial testing 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (modified FOLFIRINOX), NALIRIFOX does not seem to raise the bar, but rather exposes patients and health-care systems to financial toxicities.

    • Christopher Nevala-Plagemann
    • Ignacio Garrido-Laguna
    News & Views
  • T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.

    • David H. Aggen
    • Jonathan E. Rosenberg
    News & Views
  • A recent study reported the development and validation of the Liver Artificial Intelligence Diagnosis System (LiAIDS), a fully automated system that integrates deep learning for the diagnosis of liver lesions on the basis of contrast-enhanced CT scans and clinical information. This tool improved diagnostic precision, surpassed the accuracy of junior radiologists (and equalled that of senior radiologists) and streamlined patient triage. These advances underscore the potential of artificial intelligence to enhance hepatology care, although challenges to widespread clinical implementation remain.

    • Jeong Min Lee
    • Jae Seok Bae
    News & Views
  • The composition of the gut microbiota has emerged as a tumour-extrinsic factor that modulates response to immune-checkpoint inhibitors (ICIs), although the lack of consistency in microbiota signatures across studies has limited their value as reliable biomarkers. Herein, we discuss a recent study in which longitudinal microbiome profiling identified several taxa that are persistently enriched in patients with melanoma and a favourable response to ICIs.

    • Saman Maleki Vareki
    • Diwakar Davar
    News & Views
  • The benefits and potential harms of mammography-based screening for breast cancer are often a matter of debate. Here, I discuss the promises and limitations of a recent study that tested an artificial intelligence-based tool for the detection of breast cancer in digital mammograms in a large, prospective screening setting.

    • Despina Kontos
    News & Views
  • Durable responses with first-line platinum-based chemotherapy for advanced-stage urothelial carcinoma are rare, and patient outcomes are poor. Recently, CheckMate 901 became the first phase III trial to establish a significant overall survival benefit from a combined chemoimmunotherapy approach in this disease setting. Herein, we discuss key findings from CheckMate 901 and their implications in the context of a rapidly evolving treatment landscape.

    • Nimira Alimohamed
    • Srikala S. Sridhar
    News & Views
  • Several novel personalized therapies focus on targeting neoantigens. Such strategies require the identification of suitable vaccine neoepitopes or neoantigen-specific T cell receptor (TCR) clonotypes. Herein, we discuss a recently published report that describes a combined transcriptional and phenotype signature, NeoTCRPBL, that enables the minimally invasive identification of rare neoantigen-specific TCRs from peripheral blood that might enable more-effective T cell-based therapies against cancer.

    • Marco Donia
    • Inge Marie Svane
    News & Views
  • Recent results from the phase III PHILA trial demonstrate a benefit in terms of progression-free survival derived from the addition of pyrotinib to first-line chemotherapy plus trastuzumab in patients with metastatic HER2-positive breast cancer. Dual HER2 blockade with pyrotinib and trastuzumab is an effective therapeutic strategy but might increase the risk of gastrointestinal toxicity; therefore, the risk-to-benefit ratio should be carefully evaluated.

    • Pier Paolo M. Berton Giachetti
    • Giuseppe Curigliano
    News & Views
  • Recent results from the FLAURA2 and MARIPOSA-2 trials underline the continued role of chemotherapy in the treatment of patients with EGFR-mutated non-small-cell lung cancer in the era of targeted therapies. Herein, we argue that the most appropriate and rational sequence and/or combination of therapies remains a matter of discussion.

    • Rafael Rosell
    • María González-Cao
    News & Views
  • Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with pelvic lymphadenectomy is the current standard therapy for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). A phase II trial testing treatment intensification by adding the immune-checkpoint inhibitor nivolumab to chemotherapy has yielded promising complete response rates, which suggests that bladder-preserving treatment could become attainable in selected patients. This trial heralds a new era in demonstrating the feasibility of bladder preservation for selected patients with MIBC.

    • Jakob Klemm
    • Ekaterina Laukhtina
    • Shahrokh F. Shariat
    News & Views
  • PRO-TECT is a randomized trial that innovatively integrated financial toxicity screening into a pre-existing digital symptom-monitoring programme, enabling longitudinal detection of financial toxicity. Such a strategy provides an unobtrusive and cost-effective method for early detection and mitigation of financial toxicity by aligning the needs of patients and carers with the resources available in community clinical practices.

    • Christopher T. Su
    • Veena Shankaran
    News & Views
  • Epstein–Barr virus (EBV)-based biomarkers are used for nasopharyngeal carcinoma (NPC) screening in endemic regions. A recent prospective study describes the use of a new serological biomarker, antibodies targeting the EBV protein BNLF2b, for NPC screening in >20,000 participants. This biomarker yielded both higher sensitivity and specificity for NPC detection in the screening cohort compared with the conventionally used antibodies. Herein, we highlight the key findings of this study and discuss the implications of these results.

    • W. K. Jacky Lam
    • Anthony T. C. Chan
    News & Views
  • Following the recent FDA Accelerated Approval of enfortumab vedotin (EV) plus pembrolizumab for patients with advanced-stage urothelial carcinoma who are cisplatin-ineligible, herein we highlight key clinical outcomes with this combination based on results from Cohort K of the pivotal phase Ib/II EV-103 trial. We also discuss treatment sequencing, de-escalation strategies and toxicity management as EV–pembrolizumab becomes widely used in clinical practice.

    • Pooja Ghatalia
    • Elizabeth R. Plimack
    News & Views
  • Hotspot point mutations in IDH1 occur in the vast majority of adult grade 2–3 gliomas. The understanding of their role in tumour biology continues to evolve. Therapeutic targeting of mutant IDH1 with vorasidenib demonstrated highly encouraging efficacy and minimal toxicity in a recent, randomized phase III trial involving patients with low-grade gliomas.

    • David A. Reardon
    • Daniel P. Cahill
    News & Views
  • A recent report from the ATLAS trial comparing different maintenance strategies following haematopoeitic stem cell transplantation for multiple myeloma provides an opportunity to explore various themes of critical appraisal, including end points, the equipoise of trial design, and the part censoring can play in the validity of results.

    • Ghulam Rehman Mohyuddin
    • Tomer Meirson
    News & Views
  • Planning for a pregnancy in patients receiving adjuvant endocrine therapy following a diagnosis of hormone receptor (HR)-positive early stage breast cancer is challenging. Recent data from the POSITIVE trial provide reassuring prospective evidence that a temporary interruption of endocrine therapy for women with HR-positive breast cancer who are trying to conceive can be considered safe in the short term for selected patients.

    • Luca Arecco
    • Matteo Lambertini
    News & Views