This week in Oncology

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Oncology. This week we're covering 10 notable papers spanning a new wave of bispecific antibodies that target both the PD-1 axis and VEGF, major guideline and strategy updates in nasopharyngeal carcinoma, breast cancer, myeloma and lung cancer, and a push to rebuild staging for the rarer thyroid cancers. Let's dive in.

We start with the bispecific antibodies that combine immune checkpoint blockade and anti-angiogenic activity in a single molecule, a class with three early-phase reports this week across three journals. In Nature Medicine, Zhao and colleagues report a nonrandomized phase 2 trial of perioperative ivonescimab, a PD-1 and VEGF bispecific, in resectable non-small cell lung cancer [1]. In the cohort given ivonescimab with chemotherapy before surgery, about 70 percent of patients achieved a major pathological response, comfortably clearing the historical benchmark of 41 percent the investigators had set, and nearly every responder had five percent or less residual viable tumour. A small monotherapy cohort of ten patients reached a major response rate of 60 percent. Grade 3 or higher treatment-related toxicity affected roughly a third of patients, but there was no serious bleeding, no treatment-related death, and only one surgery delay attributable to treatment, which speaks to the main worry about adding VEGF blockade before an operation. In JAMA Oncology, Zhou and colleagues tested HB0025, a PD-L1 and VEGF bispecific, with platinum doublet chemotherapy in untreated, driver-negative advanced disease across 169 patients [2]. Response rates were higher at the 20 milligram per kilogram dose, reaching just under 60 percent in nonsquamous and nearly three quarters in squamous disease, and median progression-free survival ran just over a year in both histologies. Toxicity was substantial, though, with grade 3 or higher treatment-related events in roughly two thirds of patients, mostly haematologic. Moving beyond the chest, Zhang and colleagues report in The Lancet Oncology a single-arm phase 1b/2 trial of pumitamig, another PD-L1 and VEGF bispecific, plus nab-paclitaxel as first-line therapy for advanced triple-negative breast cancer [3]. Among 42 patients, close to three quarters of patients had a confirmed response, with long follow-up of about three years, no treatment-related deaths, and neutropenia and proteinuria as the main serious toxicities. Taken together, these three studies show consistent activity across tumour types, but none is randomized, all enrolled only in China, and each relies on response endpoints or historical comparisons. They support phase 3 testing, which the authors themselves call for, rather than settling where this class fits against established checkpoint inhibitor regimens.

Our second theme is nasopharyngeal carcinoma, where the Chinese Society of Clinical Oncology and ASCO have released two joint guidelines, both in the Journal of Clinical Oncology. For recurrent or metastatic disease, the panel led by Jiang recommends platinum-based chemotherapy plus a PD-1 inhibitor as preferred first-line therapy for fit patients, followed by maintenance PD-1 inhibition for up to two years [4]. Chemotherapy alone remains an option when immunotherapy is unsuitable or declined, selected responders may receive oral maintenance chemotherapy or locoregional consolidation radiotherapy, and salvage surgery or re-irradiation is recommended for selected isolated locoregional recurrences. Subsequent-line options include chemotherapy, PD-1 inhibitors and antibody-drug conjugates, and the panel explicitly calls for early palliative care alongside active treatment. The companion update for stage IB to III disease, led by Chen, is notable for what it holds back on [5]. It endorses image-guided IMRT with MRI-based delineation, response-adapted target volumes after induction, elective nodal de-escalation in selected patients, gemcitabine-cisplatin or TPF induction, cisplatin-based concurrent chemoradiotherapy, and metronomic capecitabine for higher-risk residual disease. But although several randomized trials of PD-1 inhibitors have improved disease control in the curative setting, overall survival data remain immature, and the panel makes no recommendation for or against routinely adding immunotherapy. So the same agents are a firm first-line standard in metastatic disease yet remain an individualized decision in locally advanced disease, a contrast that reflects where the survival evidence currently stands.

The third theme is how established regimens are selected, extended and dosed. In JAMA Oncology, Zong, Carey and Abdou review first-line treatment for ERBB2-positive metastatic breast cancer [6]. They describe how the DESTINY-Breast09 result, with superior progression-free survival for trastuzumab deruxtecan plus pertuzumab, challenges the long-standing taxane-based induction and maintenance paradigm, and how maintenance options have broadened through endocrine therapy with CDK4/6 inhibition in PATINA and a triplet anti-ERBB2 approach in HER2CLIMB-05. Open questions remain on whether chemotherapy is needed, how long to continue an antibody-drug conjugate, and the role of dual blockade, and the authors stress that biomarker tools such as HER2DX and circulating tumour DNA are still investigational. In the Journal of Clinical Oncology, Sonneveld and colleagues extrapolated progression-free survival for daratumumab, bortezomib, lenalidomide and dexamethasone from the PERSEUS and CEPHEUS trials in newly diagnosed myeloma [7]. Using the best-fitting model, projected median progression-free survival was about 17 years with the quadruplet versus about 7 years with the triplet in transplant-eligible patients, and roughly 8 versus 4 years in transplant-ineligible patients. These are modelled projections, not observed data, since median progression-free survival has not been reached in either trial, so they illustrate the potential size of the benefit rather than prove it. Finally, in Clinical Cancer Research, Carrasquilla and colleagues pooled patient-level trial data for afatinib, dacomitinib, mobocertinib and osimertinib in EGFR-mutant lung cancer to ask how dosage modifications affect outcomes [8]. Dose interruptions, particularly breaks of four or more consecutive days, were more often associated with a higher risk of progression or death than dose reductions, though the effect on survival varied by drug. The analysis is exploratory and observational, vulnerable to the confounding that comes with toxicity itself, but it lends some support to the idea that reducing the dose may compromise efficacy less than stopping treatment.

Our last theme is staging for rarer thyroid cancers, with two large international efforts from the same group led by Shi. In the Journal of Clinical Oncology, a consortium spanning 43 centres in 15 countries analyzed about 2,600 patients with medullary thyroid carcinoma [9]. Under the current AJCC eighth edition, stages II and III did not separate meaningfully from stage I, whereas the proposed system, which also upgrades level VII nodal disease to N1c, produced a steadily rising risk of disease-specific death across stages and better discrimination, with the findings also examined in a SEER cohort. In JAMA Oncology, the same investigators propose the first dedicated staging system for poorly differentiated thyroid cancer, using about a thousand patients from 91 centres [10]. Again level VII nodal disease was reclassified to N1c, the share of patients labelled stage I fell from about 44 to about 25 percent, and discrimination improved modestly in the development cohort. In the smaller SEER validation cohort, however, the gain was small and not clearly significant. Both proposals are retrospective and come from a single research group, so they are a strong case for the next AJCC revision rather than a replacement for current staging today.

If you only have time for one paper this week, make it the CSCO-ASCO update on stage IB to III nasopharyngeal carcinoma [5]. It consolidates the curative-intent standard across radiotherapy, induction and adjuvant therapy, and it deliberately leaves open whether PD-1 inhibitors belong in that pathway until survival data mature.

That's your roundup for This Week in Oncology. The full transcript and references are available on the episode page. See you next week.

If this weekly briefing is useful, follow the show in your podcast app so new episodes arrive automatically. And a quick rating on Apple Podcasts or Spotify helps other physicians discover the show.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.