A survival gain, a first DNA immunotherapy and a null trial: 4 stories

In small-cell lung cancer, adding tarlatamab to maintenance therapy raised median survival to 21 months

On 24 October 2026 the New England Journal of Medicine published the interim analysis of DeLLphi-305, an international phase 3 trial in 563 people with extensive-stage small-cell lung cancer whose disease had not progressed after first-line chemotherapy with immunotherapy. They were randomised to maintenance treatment with durvalumab alone or with durvalumab plus tarlatamab, a bispecific antibody that brings the patient's T cells to the DLL3 protein on tumour cells.

Median overall survival was 21.1 months with the combination and 12.7 months with durvalumab alone (hazard ratio for death 0.42, 95% CI 0.32–0.54); median progression-free survival was 7.4 versus 1.9 months. The authors note that median survival in this cancer is usually about 12 to 13 months, which puts the size of the gap in context.

This is an interim analysis of an open-label trial, with a median follow-up of about 16 months, funded by Amgen and AstraZeneca. Adverse events of grade 3 or higher occurred in 46.8% of patients on the combination and 40.6% on durvalumab alone, and cytokine release syndrome, mostly grade 1 or 2, in nearly half of those on the combination. Tarlatamab had earlier been shown to extend survival as second-line treatment; as maintenance after first-line therapy the combination is still investigational.

The FDA gave accelerated approval to the first plasmid DNA immunotherapy, for a rare HPV disease of the airway

On 30 October 2026 the US Food and Drug Administration granted accelerated approval to Voceryq (Inovio Pharmaceuticals) for adults with recurrent respiratory papillomatosis, a rare disease in which human papillomavirus types 6 and 11 cause wart-like growths in the airway, most often around the larynx, particularly the vocal cords. Surgery removes the growths but not the virus, so many patients need repeated operations for years.

The therapy delivers two small rings of DNA, plasmids, into the body's cells: one carries instructions for HPV proteins, the other for the immune signalling molecule IL-12. It is designed to stimulate the immune system to respond to and attack cells infected with these HPV types. It is injected into a muscle with a device that applies brief electrical pulses, electroporation, to let the DNA into cells. According to the FDA, it is the first plasmid DNA-based immunotherapy approved in the US.

The decision rests on an open-label multicentre trial in 32 adults who had needed at least two surgeries in the previous 12 months. Of the 26 patients who had had at least three, 7 (27%) needed no surgery in the first year after treatment. Fewer surgeries is an intermediate endpoint, so the approval is accelerated and the company must confirm the clinical benefit in further trials. The most common side effects were injection-site reactions, headache, fatigue, high blood pressure, nausea and dizziness.

In people over 80 with kidney disease, starting an SGLT2 inhibitor was linked to lower mortality, and to some risks

At ASN Kidney Week 2026 in Denver, researchers from Hannover Medical School presented an analysis of electronic health records of 10,076 adults aged 80 or older with chronic kidney disease. Over two years of follow-up, starting an SGLT2 inhibitor was linked to an 18% lower risk of death from any cause and a 22% lower risk of major adverse kidney events.

The picture is not one-sided. There was no significant effect on major cardiovascular events overall, and the drugs were associated with higher risks of specific cardiac events, such as heart attack and acute heart failure, as well as acute kidney injury. People this old are rarely included in large randomised trials, which is the gap the authors set out to fill with real-world data.

The study is observational, and the source available so far is the society's press release of 24 October about the congress presentation. It cannot show that the drugs caused the differences: people who were prescribed them may have differed from those who were not. The authors themselves call for an individual weighing of benefit and risk with close monitoring in this age group.

Adding enzalutamide to radiotherapy did not extend metastasis-free survival in high-risk localised prostate cancer

On 24 October 2026 the Journal of Clinical Oncology published ENZARAD, a phase 3 trial led by the ANZUP cancer trials group in 802 men with high-risk localised or locally advanced prostate cancer. All received radiotherapy and two years of androgen deprivation therapy, and were randomised to add either enzalutamide for two years or an older antiandrogen for six months.

After a median follow-up of 92 months, 8-year metastasis-free survival on conventional imaging was 74% with enzalutamide and 72% with the older drug (hazard ratio 0.88, 95% CI 0.67–1.15; P=0.34), and overall survival did not improve either. Grade 3–5 adverse events were reported in 185 participants in each arm.

In a prespecified subgroup of 324 men with planned radiotherapy to the pelvic lymph nodes, enzalutamide was associated with a possible benefit (hazard ratio 0.47). The primary endpoint was not met, so this prespecified subgroup finding needs confirmation in further studies; the trial was also open-label. For the group as a whole, enzalutamide added no measurable gain on top of standard radiotherapy and hormone therapy.

This material is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Pérol M, Yoshida T, Ahn MJ, et al. Tarlatamab-Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2026. PMID 42929702, doi:10.1056/NEJMoa2609482, NCT06211036

• U.S. Food and Drug Administration. FDA approves first plasmid DNA-based immunotherapy for adults with recurrent respiratory papillomatosis. 30 October 2026. FDA, NCT04398433

• American Society of Nephrology. Advanced age does not limit the benefits of sodium-glucose cotransporter 2 inhibitors in chronic kidney disease. Press release, 24 October 2026. ASN

• Williams S, Sweeney CJ, Thomas H, et al. ENZARAD (ANZUP 1303): Phase 3 Trial of Enzalutamide With Androgen Deprivation Therapy and Radiation Therapy in High-Risk Localized or Locally Advanced Prostate Cancer. J Clin Oncol. 2026. PMID 42921729, doi:10.1200/JCO-26-01794