This Week in Oncology — May 28, 2026

Welcome to This Week in Oncology. This week we're covering 10 notable papers spanning new therapeutic strategies in solid tumors, innovations in cell therapy, and fundamental mechanisms of cancer biology. We'll also flag two key guideline updates from ASCO. Let's dive in.

New Therapeutic Strategies in Solid Tumors

First, we'll look at three clinical trials that could change practice in gastrointestinal and bladder cancers.

Starting in gastroesophageal adenocarcinoma, a phase 3 trial published in The New England Journal of Medicine evaluated a new first-line option for HER2-positive disease [4]. This study, called HERIZON-GEA-01, randomized over 900 patients with previously untreated, advanced HER2-positive gastroesophageal adenocarcinoma into three arms: standard trastuzumab plus chemotherapy, the bispecific antibody zanidatamab plus chemotherapy, or zanidatamab plus chemotherapy and the PD-1 inhibitor tislelizumab. The primary endpoints were progression-free survival and overall survival.

Results

At a median follow-up of about 26 months, both zanidatamab-containing arms significantly improved progression-free survival compared to the trastuzumab arm. The median PFS was 12.4 months for both zanidatamab arms, compared to just 8.1 months with standard therapy. This translates to a reduction in the risk of progression or death by about 35 percent. For overall survival, the triplet combination of zanidatamab, tislelizumab, and chemotherapy was superior to trastuzumab plus chemo, with a median overall survival of 26.4 months versus 19.2 months. However, at this interim analysis, the overall survival benefit for zanidatamab plus chemotherapy alone compared to trastuzumab plus chemotherapy was not statistically significant. In terms of safety, grade 3 or higher adverse events were most common in the triplet arm, at 83 percent, driven largely by diarrhea, which occurred in nearly 25 percent of patients in that group, compared to 20 percent with zanidatamab-chemo and 13 percent with trastuzumab-chemo.

Conclusions

These results establish zanidatamab plus chemotherapy, with or without tislelizumab, as a new standard of care that improves progression-free survival in first-line HER2-positive gastroesophageal adenocarcinoma. The addition of tislelizumab also provides a significant overall survival benefit.

Next, a paper in Nature Medicine reports on a successful targeted therapy for a rare type of gastrointestinal stromal tumor, or GIST [6]. While most GISTs are driven by KIT or PDGFRA mutations, about 10 to 15 percent have functional loss of the succinate dehydrogenase, or SDH, complex. This leads to widespread DNA hypermethylation and aberrant activation of an FGFR1 signaling loop. This phase 2 trial evaluated the pan-FGFR inhibitor rogaratinib in 24 patients with advanced SDH-deficient GIST. The primary objective was objective response rate. The study found that 10 of the 24 patients, or about 42 percent, achieved a partial response. The median progression-free survival was an impressive 31 months, with a 1-year PFS rate of over 77 percent. Toxicities were manageable, with the most common being hyperphosphatemia, fatigue, and diarrhea. The consistent observation of elevated phosphorus levels confirmed target engagement of FGFR1. This trial is a powerful demonstration of a targeted therapy designed to counteract an epigenetic mechanism of oncogene activation.

Finally in this section, we turn to muscle-invasive bladder cancer, or MIBC. The NEMIO study, published in the Journal of Clinical Oncology, evaluated neoadjuvant dose-dense MVAC chemotherapy combined with immunotherapy [7]. This was a randomized, noncomparative phase 2 trial in cisplatin-eligible patients planned for radical cystectomy. Patients received four cycles of ddMVAC plus the PD-L1 inhibitor durvalumab, either with or without the CTLA-4 inhibitor tremelimumab. The coprimary endpoints were pathologic complete response, or pCR, and severe treatment-related adverse events.

Results

The study was considered positive if the pCR rate was at least 45 percent and the rate of grade 3 or higher TRAEs was 30 percent or less. The results showed a pCR rate of about 49 percent with the durvalumab doublet and 46 percent with the durvalumab-tremelimumab triplet, meeting the efficacy endpoint. However, the rate of grade 3 or higher TRAEs was about 41 percent overall, exceeding the prespecified safety threshold. Toxicity was notably higher with the triplet regimen, at nearly 50 percent, compared to about 30 percent with the doublet. An exploratory analysis showed a striking difference based on PD-L1 status: pCR rates were around 68 percent in PD-L1-high tumors, versus just 33 percent in PD-L1-low or negative tumors. Early survival data is encouraging, with two-year event-free survival around 75 percent and overall survival around 85 percent in both arms. The key takeaway is that adding tremelimumab increased toxicity without improving pCR rates. The authors conclude that neoadjuvant ddMVAC plus durvalumab is a promising strategy, particularly for PD-L1 high patients, and warrants further study in comparative trials.

Innovations in Cell Therapy

Next, we turn to cell therapy, with a clinical update in multiple myeloma and a key preclinical finding that could boost efficacy in solid tumors.

A phase 1 trial published in Science Translational Medicine presents data on durcabtagene autoleucel, a novel BCMA-targeted CAR T-cell therapy for relapsed or refractory multiple myeloma [5]. A major challenge with current CAR T-cell therapies is the long manufacturing time, which can lead to T-cell exhaustion and limit patient access. This new product uses a rapid manufacturing platform designed to preserve T-cell stemness.

Results

The therapy was successfully manufactured for all 55 patients in the study, with a median vein-to-vein time of just 24 days. Patients received a single infusion at one of four dose levels. The results were impressive: the overall response rate was 98 percent, with 55 percent of patients achieving a stringent complete response. Among evaluable patients, 80 percent achieved minimal residual disease negativity. The safety profile was as expected, with no reports of delayed neurotoxicity. Analysis of the final product confirmed the preservation of a stem-like phenotype. These promising phase 1 results have prompted a phase 2 trial to further evaluate this therapy in heavily pretreated patients.

Building on the theme of improving cell therapy, a paper in Nature Cancer provides a compelling mechanism for combining radiotherapy with CAR T-cells in solid tumors [10]. High tumor burden often limits CAR T-cell efficacy, but dose escalation is capped by off-tumor toxicity. This study used mouse models of metastatic lung adenocarcinoma and melanoma to investigate how radiation might help. They found that a single dose of 8 Gray of tumor irradiation significantly enhanced CAR T-cell persistence and efficacy. The key mechanism depended on dendritic cells. Radiation promoted a process called trogocytosis, where dendritic cells essentially 'dress' themselves with tumor antigens taken from cancer cells. These antigen-dressed dendritic cells then directly expanded the CAR T-cell population through the chimeric antigen receptor itself. Without functional dendritic cells, radiation failed to sustain the CAR T-cell response. Importantly, this effect was localized: CAR T-cell numbers increased within the irradiated tumors but not in adjacent normal lung tissue that also expressed the target antigen. This suggests the combination can improve tumor control without increasing toxicity. These data provide a strong mechanistic rationale for combining radiation with CAR T-cell therapy to widen the therapeutic window in solid tumors.

Foundational Discoveries in Cancer Biology

Finally, we'll cover three papers from Nature and Cell that uncover fundamental mechanisms with future therapeutic potential.

First, a study in Nature reveals that human hematopoietic stem cells, or HSCs, can remember past inflammatory stress [1]. Using xenograft models, researchers identified a distinct subset of HSCs they term 'HSC inflammatory memory', or HSC-iM. These cells retain a molecular memory of previous inflammation, causing them to become quiescent and restrain blood production. This HSC-iM molecular program was found in humans across a range of conditions, from recovery from COVID-19 to sickle cell disease, aging, and clonal hematopoiesis. Interestingly, clonal hematopoiesis mutations in these memory stem cells seemed to counteract the inflammatory stress, promoting activation and differentiation. The pro-inflammatory program from these stem cells could also be transmitted to their progeny, the differentiated immune cells. Most clinically relevant, enrichment of this HSC-iM program in circulating blood cells was associated with a higher risk score for all-cause mortality in large population cohorts. This work identifies a new, clinically relevant stem cell subset that links inflammation, aging, and malignancy.

Also in Nature, a second paper uncovers a novel metabolic mechanism that drives DNA repair [2]. It’s well known that cancers with homologous recombination, or HR, deficiency are sensitive to DNA-damaging agents. This study investigated metabolic factors that might drive resistance in HR-proficient cancers. The authors found that the metabolite alpha-ketoglutarate, or αKG, is critical. Using a CRISPR screen, they identified an enzyme called TMLHE as essential for the survival of HR-proficient cells treated with DNA-damaging agents. TMLHE is the first enzyme in carnitine synthesis. The study showed that αKG-dependent carnitine synthesis is required for histone acetylation, which in turn promotes HR-mediated DNA repair. In patient samples, high levels of TMLHE or its product, acetylcarnitine, correlated with worse progression-free survival in patients treated with DNA-damaging agents. This work provides a metabolic avenue for potentially inducing HR deficiency and sensitizing resistant cancers to treatment.

And in the journal Cell, researchers describe a new regulatory mechanism for one of oncology’s most notorious drivers: KRAS [3]. They discovered that KRAS can form condensates in the cytoplasm through a process called liquid-liquid phase separation, or LLPS. This process is driven by farnesylation, a lipid modification on the KRAS protein. These KRAS condensates were associated with advanced stages and poor outcomes in colon cancer. Functionally, the condensates allow KRAS to efficiently interact with an enzyme that processes it, facilitating its trafficking to the cell membrane and amplifying its signaling. In a therapeutic screen of FDA-approved drugs, the authors found that statins, particularly pitavastatin, disrupt these KRAS condensates by inhibiting farnesylation. This suppressed colon cancer growth and even enhanced the efficacy of a KRAS G12C inhibitor. These findings reveal a new layer of KRAS regulation and suggest a promising and readily available therapeutic strategy to target it.

Guideline Updates

And a quick note for our listeners treating lung cancer. The American Society of Clinical Oncology has published its latest living guideline updates for the treatment of Stage IV non-small cell lung cancer. Two separate documents are available in the Journal of Clinical Oncology: one covering therapy for patients with driver alterations [8], and another for patients without driver alterations [9]. We recommend reviewing these for the most current treatment recommendations.

If you only have time for one paper this week, make it the HERIZON-GEA-01 trial in The New England Journal of Medicine [4]. This phase 3 study establishes a new, superior first-line standard of care for patients with HER2-positive advanced gastroesophageal adenocarcinoma, replacing a regimen that has been in place for over a decade.

Here are the key takeaways from this week in Oncology.

First: In first-line HER2-positive gastroesophageal adenocarcinoma, adding zanidatamab to chemotherapy improves progression-free survival over trastuzumab plus chemotherapy. The addition of tislelizumab to that backbone also improves overall survival. [4]

Second: In muscle-invasive bladder cancer, neoadjuvant dose-dense MVAC plus durvalumab yields high pathologic complete response rates, particularly in PD-L1-high tumors, without the added toxicity of tremelimumab. [7]

Third: For the rare subset of SDH-deficient GIST, the FGFR inhibitor rogaratinib shows a high response rate and durable progression-free survival, validating a targeted therapy for an epigenetically driven cancer. [6]

Fourth: A rapid-manufacturing platform for BCMA CAR-T, durcabtagene autoleucel, shows very high response rates in relapsed and refractory myeloma, with a final product that preserves T-cell stemness. [5]

Fifth: Preclinically, tumor irradiation appears to enhance CAR-T persistence and efficacy by promoting antigen dressing of dendritic cells, providing a strong rationale for this combination therapy in solid tumors. [10]

That's your roundup for This Week in Oncology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.