In 2023, a decade after granting Accelerated Approval to the first-in-class BTK inhibitor ibrutinib for the treatment of mantle cell lymphoma, the FDA requested this indication be withdrawn. Herein, we discuss the seemingly inconsistent results from the SHINE and TRIANGLE trials, which relate to the distinct patient populations of these trials, and posit that regulatory approaches should take these

Children with recurrent high-grade glioma typically receive combination chemotherapy, although these regimens provide limited benefit and are highly toxic. Approximately 5–10% of these patients have BRAFV600E-mutant tumours. Now, data from a phase II trial demonstrate the efficacy of the BRAF inhibitor dabrafenib combined with the MEK inhibitor trametinib in this patient subset.

Patients with advanced-stage HR+, HER2– breast cancer and disease progression on endocrine therapy plus a targeted therapy (typically a CDK4/6 inhibitor) usually receive single-agent chemotherapy, which is often ineffective. Now, mature data from the phase III TROPiCS-02 trial demonstrate that sacituzumab govitecan, an antibody–drug conjugate, improves overall survival (OS) relative to single-agent

Over the past few years, several studies have demonstrated the efficacy of sotorasib and adagrasib in patients with KRASG12C-mutant solid tumours, leading to the FDA approval of both inhibitors for patients with advanced-stage non-small-cell lung cancer (NSCLC) harbouring this alteration and who have received at least one prior line of therapy. However, single-agent treatment with these agents provides

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

Historically, therapy for advanced-stage hepatocellular carcinoma (HCC) was almost entirely dependent on VEGFR-directed multi-targeted tyrosine-kinase inhibitors (TKIs), predominantly sorafenib. Since 2020, however, non-TKI, immune-checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care. Now, use of a novel ICI and TKI regimen in this setting has been shown to prolong

Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer, with recurrence rates of 27–77% after surgery with or without adjuvant radiotherapy; however, no standard-of-care systemic adjuvant therapy has been established. Immune-checkpoint inhibitors are highly efficacious in patients with advanced-stage, unresectable MCC. Now, data from the phase II ADMEC-O trial suggest that adjuvant

Although 25% of patients with renal cell carcinoma (RCC) have a non-clear-cell histology, this population has typically not been included in pivotal phase III trials in advanced-stage disease. As a result, optimal treatment options for these patients are not well established. Now, results from the single-arm phase II KEYNOTE-B61 trial, involving only patients with advanced-stage non-clear-cell RCC

Patients with papillary craniopharyngioma often survive several decades following diagnosis. Nonetheless, owing to the anatomical location, typically at the midline or in or above the sella turcica, patients will often present with headaches, peripheral vision loss, endocrine disorders and other neurological impairments that arise from the compression of critical structures. Surgery and/or radiotherapy

The pivotal trials supporting the use of anti-PD-(L)1 antibodies, with or without chemotherapy, as the standard-of-care first-line treatment for advanced-stage non-small-cell lung cancer (NSCLC) excluded patients ineligible for platinum-based doublet chemotherapy. As a result, many of these patients continue to receive only single-agent chemotherapy. Now, the phase III IPSOS trial provides confirmation

Crossover in a randomized trial can skew the interpretation of the efficacy of a cancer drug. In this Comment, I use examples from clinical trials presented at the 2023 ASCO annual meeting to highlight why ‘allowing’ crossover in randomized trials testing cancer drugs is problematic, and propose that crossovers should either be mandated or prohibited depending on the context.

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.

Incorporating anti-angiogenic agents such as bevacizumab, aflibercept, ramucirumab and regorafenib across various lines of treatment for metastatic colorectal cancer (mCRC) improves overall survival (OS). Now, results from the phase III FRESCO-2 trial support the novel, highly selective, oral VEGFR inhibitor fruquintinib as a new therapeutic option that might further expand the role of angiogenesis

Telemedicine represents the practical embodiment of patient-centred oncology care, a concept that has become increasingly popular in the past few years. Yet despite the demonstrated benefits of telemedicine, its longitudinal adoption remains limited. Herein we discuss some of the potential challenges that telemedicine faces, as we underutilize this approach relative to its anticipated value.

COSMIC-313 combines all of the approved drugs against actionable targets in renal cell carcinoma into one triplet regimen. Although this approach has greater clinical efficacy than one of the standard-of-care doublet therapies, toxicities can limit adequate drug administration and, thus, we argue that this regimen should not yet be adopted. We also discuss ongoing investigations of other triplet regimens

The 2023 ASCO Annual Meeting brought together 43,000 oncology professionals, 36,000 of them in person in Chicago. ‘Partnering with patients: the cornerstone of cancer care and research’ was the principle at the centre of this year’s programme.

In April 2022, the FDA approved the autologous CD19-targeted chimeric antigen receptor (CAR) T cell product axicabtagene ciloleucel (axi-cel) as a second-line therapy for patients with relapsed and/or refractory large B cell lymphoma (LBCL) after the primary efficacy analysis of the ZUMA-7 revealed that this product improves event-free survival (EFS) relative to standard of care (SOC): high-dose chemotherapy

In December 2020, the FDA approved adjuvant therapy with the third-generation EGFR tyrosine-kinase inhibitor (TKI) osimertinib for patients with surgically resected stage II–IIIA non-small-cell lung cancer (NSCLC) harbouring certain EGFR alterations (exon 19 deletions or exon 21 L858R) based on disease-free survival (DFS) data from the phase III ADAURA trial. Now, long-term follow-up data from this

Patients with advanced-stage HR+, HER2– breast cancer with disease progression on first-line therapy have a poor prognosis, with limited therapeutic options available. Now, data from the phase III CAPItello-291 trial demonstrate that the AKT inhibitor capivasertib, in combination with the selective oestrogen-receptor degrader fulvestrant, prolongs progression-free survival (PFS) in this setting.

The FDA Accelerated Approval pathway, which has been pivotal in enabling early access to new oncology drugs over the past three decades, has recently come under increased scrutiny. New draft guidance published in March 2023 offers several possible solutions to improve this pathway, with the ultimate goal of improving outcomes for patients with cancer, but might also have important limitations.

FLT3 internal tandem duplication (FLT3-ITD) occurs in ~25% of patients with acute myeloid leukaemia (AML) and confers a poor prognosis. New data from the phase III QuANTUM-First trial demonstrate that adding the selective FLT3 inhibitor quizartinib to first-line therapy for this subset of patients improves overall survival (OS).

Patients with chronic lymphocytic leukaemia (CLL) typically receive first-line chemoimmunotherapy comprising the anti-CD20 antibody rituximab plus either fludarabine and cyclophosphamide or bendamustine for patients ≤65 or >65 years of age, respectively. In the past decade, several agents have been approved for this malignancy, including the BTK inhibitor ibrutinib, the BCL2 antagonist venetoclax and

Patients with metastatic colorectal cancer (CRC) with disease progression on first-line 5-fluorouracil-based chemotherapy regimens typically receive alternative chemotherapy regimens, including trifluridine plus tipiracil (FTD–TPI), although the effectiveness of combining targeted therapies with this regimen remains uncertain. Now, data from the phase III SUNLIGHT trial demonstrate improved outcomes

The antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) is a highly effective second-line therapy for patients with metastatic HER2-positive breast cancer. Nonetheless, the activity of this agent in patients with disease progression on trastuzumab emtansine (T-DM1), the previous second-line standard of care, remains unknown. Now, data from the phase III DESTINY-Breast02 trial provide evidence

BRAFV600E, the most common BRAF mutation, can be detected in a variety of malignancies. These include several rare cancer types, such as adenocarcinomas of the small intestine (ASI), anaplastic thyroid cancer (ATC), biliary tract cancers (BTC), gastrointestinal stromal tumours (GIST), hairy cell leukaemia (HCL), high-grade gliomas (HGG), low-grade gliomas (LGG) and multiple myeloma (MM). Now, data

Infants (<1 year of age at diagnosis) with KMT2A-rearranged acute lymphoblastic leukaemia (ALL) have a poor prognosis with standard-of-care therapy (6-year overall survival (OS) 58%). Now, data from a phase II study demonstrate that the addition of a single cycle of the CD19 × CD3-targeted bispecific antibody blinatumomab to standard-of-care chemotherapy is well-tolerated and improves short-term survival

Evidence indicates that patients with advanced-stage cutaneous T cell lymphomas (CTCLs) might benefit from allogeneic haematopoietic stem-cell transplantation (HSCT); however, the data come from single-arm, mostly retrospective case series. Now, results from the prospective, controlled CUTALLO study confirm that HSCT improves outcomes.

Patients with HER2– advanced-stage gastric or gastro-oesophageal junction (G/GEJ) cancers typically receive 5-fluorouracil, folinic acid and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX), although survival with these regimens tends to be poor. Evidence suggests that CLDN18.2, a gastric-specific isoform of the tight-junction protein claudin 18 that is overexpressed in the majority of

This year’s American Association for Cancer Research (AACR) annual meeting in Orlando, Florida, featured around 21,000 in-person attendees, plus a further 5,000 who attended online only.

Conventional chemotherapy for advanced-stage biliary tract cancers (BTCs) is associated with median overall survival (OS) durations of <12 months. In 2022, however, the FDA approved durvalumab in combination with first-line chemotherapy based on a significant OS improvement in the phase III TOPAZ-1 trial. Now, data from the phase III KEYNOTE-966 trial of pembrolizumab cement chemoimmunotherapy as the

Neuroblastoma accounts for >10% of all cancer-related deaths in the paediatric population. Among patients with relapse of high-risk neuroblastoma, 5-year overall survival is <20%. Now, a phase I/II trial has revealed the promising activity of GD2-CART01, an autologous T cell product expressing both a GD2-directed chimeric antigen receptor (CAR) with 4-1BB and CD28 co-stimulatory domains and an inducible

Transgender patients are a marginalized group for whom current standards of oncology have yet to be optimized. In this Comment, we highlight opportunities for transgender-inclusive and transgender-specific practices across the cancer care continuum and identify evidence gaps that will need to be filled to attain optimal care for transgender populations.

Anti-PD-(L)1 antibodies in combination with a VEGF tyrosine-kinase inhibitor (TKI) or ipilimumab are the standard-of-care first-line therapy for patients with advanced-stage clear cell renal cell carcinoma (ccRCC). Nonetheless, treatment options for patients who fail to respond to, or have disease progression on, such regimens are currently limited. Now, data from a phase II study testing the HIF2α