This Week in Oncology — Jun 6, 2026

Welcome to This Week in Oncology. This week we're covering 10 notable papers spanning major updates in lung cancer, novel therapeutic strategies for tough-to-treat malignancies, and new insights into tumor biology and supportive care. Let's dive in.

We begin this week with lung cancer, where a long-term follow-up from the ASTRUM-005 trial was published in JAMA Oncology [6]. This was a phase 3 study in previously untreated extensive-stage small cell lung cancer, which confirmed the durable benefit of adding the PD-1 inhibitor serplulimab to standard carboplatin and etoposide. With a median follow-up of over 42 months, the addition of serplulimab extended median overall survival to 15.8 months compared to 11.1 months with chemotherapy alone, which translates to a 40% reduction in the risk of death. Even more impressively, the 4-year overall survival rate was 21.9% in the serplulimab arm, almost triple the 7.2% seen in the placebo group. This long-term data strongly supports serplulimab plus chemotherapy as a first-line standard of care. Shifting from treatment to prevention, a paper in Cell explores a new way to identify individuals at high risk for developing lung cancer [3]. Researchers used machine learning to develop a 14-protein plasma signature that could predict lung cancer more than five years before a clinical diagnosis. This signature was found to be elevated in smokers and those exposed to particulate matter. The key clinical insight here relates to the CANTOS trial, where IL-1 beta inhibition reduced lung cancer incidence but required treating a large number of people. The new protein signature was able to identify a subgroup of patients in CANTOS who seemed to derive the most benefit, potentially lowering the number needed to treat and paving the way for more targeted cancer prevention strategies.

Next, we turn to a series of papers on novel strategies for difficult cancers. In the Journal of Clinical Oncology, we have a first-in-human phase 1 trial of a new CAR T-cell therapy for metastatic colorectal cancer [4]. The therapy targets GUCY2C, an antigen expressed consistently in CRC. In 20 heavily pretreated patients, the treatment showed an acceptable safety profile, though grade 3 diarrhea was common, occurring in 55% of patients. The overall response rate was 26.3%, but in the dose level selected for expansion, the response rate was 40%, with a median progression-free survival of 7 months. For a population with very limited third-line options, these early results are quite promising. For another devastating diagnosis, leptomeningeal disease, a phase 1 trial in Nature Cancer explored intrathecal administration of nivolumab [1]. In 24 patients with LMD from various solid tumors, intraventricular nivolumab was found to be safe and feasible, with a recommended dose of 50 mg established for the expansion cohort. While this was primarily a safety study, the median overall survival of 6.6 months, with a 1-year survival rate of 33%, is noteworthy in a patient population with a historically dismal prognosis. In hematologic malignancy, The New England Journal of Medicine reports on a completely oral regimen for older or unfit patients with newly diagnosed AML [9]. The ASCERTAIN-V trial combined oral decitabine-cedazuridine with oral venetoclax. The study confirmed no significant drug-drug interactions. In the phase 2b portion, the all-oral combination achieved a complete response rate of 47%, and a median overall survival of 15.5 months. These results are comparable to the standard intravenous regimens, but offer a profound improvement in patient convenience and quality of life by eliminating the need for frequent clinic visits. And also from The New England Journal of Medicine, a trial on IgG4-related disease, a fibroinflammatory condition often managed by hematologist-oncologists [10]. The study tested obexelimab, a monoclonal antibody that inhibits B-cells without depleting them. Compared to placebo, weekly obexelimab significantly reduced the risk of disease flares by more than half and allowed for successful glucocorticoid tapering, with patients on obexelimab achieving complete remission at a significantly higher rate.

Our final theme covers deep dives into tumor biology and a practice-changing supportive care study. Published in the Journal of Clinical Oncology, a non-inferiority trial addressed a common clinical question: can we reduce dexamethasone for chemotherapy-induced nausea and vomiting prophylaxis in patients receiving highly emetogenic chemotherapy? [5]. The trial randomized patients who were already receiving NEPA and olanzapine to three arms: a standard 4-day dexamethasone schedule, a single 6mg dose on day 1, or no dexamethasone at all. The results showed that both the single-dose and dexamethasone-free regimens were non-inferior to the standard schedule in preventing emesis. This is a crucial finding, as it allows clinicians to significantly reduce steroid exposure and its associated toxicities, a particularly important consideration in the era of chemo-immunotherapy. Moving to the lab, two papers in Nature and Cancer Cell provide new insights into tumor evolution. One study, published in Nature, used single-cell analysis of IDH-mutant gliomas from patients over time to understand drivers of progression [8]. It identified two main paths to recurrence: one driven by new genetic alterations that cause cells to become less differentiated and more proliferative, and a second, independent path where tumors develop a mesenchymal-like state, which coincides with increased macrophage infiltration in the tumor microenvironment. This highlights both cell-intrinsic and extrinsic factors in glioma progression. A related story of tumor evolution comes from Cancer Cell, which investigated the complex role of hypoxia in clear cell renal cell carcinoma treated with VEGFR-TKIs and immunotherapy [2]. The study found that treatment-induced hypoxia, which reflects successful cell killing, is a good prognostic sign. However, pre-existing hypoxia in the tumor before treatment predicted worse outcomes. This paradoxical role of hypoxia helps explain some of the complexities of response and resistance to combination therapies in kidney cancer. Finally, a basic science paper in Nature identified spermine as an endogenous iron chelator that can suppress ferroptosis, a type of iron-dependent cell death [7]. Inhibiting spermine synthesis triggered ferroptosis and impaired liver cancer development in preclinical models, uncovering a fundamental metabolic circuit with potential therapeutic implications.

If you only have time for one paper this week, make it the study by Meng and colleagues in the Journal of Clinical Oncology on reducing dexamethasone for CINV prevention [5]. This is a pragmatic, practice-changing trial showing that with a modern antiemetic backbone of NEPA and olanzapine, we can safely de-escalate and even omit steroids for patients on highly emetogenic chemotherapy, directly reducing toxicity without compromising efficacy.

Here are the key takeaways from this week in Oncology: First, for extensive-stage small cell lung cancer, adding serplulimab to first-line chemotherapy provides a durable, long-term survival benefit, with nearly one in four patients alive at four years. Second, for older or unfit patients with newly diagnosed AML, a new all-oral regimen of decitabine-cedazuridine plus venetoclax provides efficacy comparable to the intravenous standard of care, representing a major step forward for patient quality of life. Third, you can safely and effectively reduce or omit dexamethasone for CINV prevention in patients receiving highly emetogenic chemotherapy, as long as they are on a backbone of NEPA and olanzapine. This is non-inferior to standard 4-day dexamethasone and reduces steroid-related side effects. Fourth, early data for GUCY2C-targeted CAR T-cells are showing promising response rates in heavily pretreated metastatic colorectal cancer, opening a potential new therapeutic avenue for this disease. And finally, for patients with IgG4-related disease, the B-cell inhibitor obexelimab significantly reduces disease flares and the need for chronic glucocorticoids.

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.

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