Spacing Immunotherapy to Every 12 Weeks Failed in the MOIO Trial. More Patients Died.
The phase 3 MOIO trial stopped early after deaths reached 19.9 percent with 12-weekly checkpoint inhibitors versus 10.5 percent with standard dosing.
Giving checkpoint inhibitors every 12 weeks to patients responding after six months of standard dosing failed to prove noninferior and was associated with more deaths in the phase 3 MOIO trial, stopped early and presented Oct. 26 at ESMO.
Gwenaëlle Gravis, M.D., of Institut Paoli-Calmettes in Marseille presented the results (LBA10) in the European Society for Medical Oncology's Presidential Symposium III. The trial is an academic study sponsored by Unicancer, the French network of cancer centers, according to the published protocol in BMC Cancer. The results below come from reports of the presentation by Targeted Oncology and OncoDaily; no full paper is available yet, and the two reports round some figures differently.
What did MOIO test?
MOIO asked whether patients in partial or complete response after six months of a PD-1 or PD-L1 inhibitor could safely receive the same dose every three months instead. Eligible tumors included lung, renal, bladder, head and neck, triple-negative breast, Merkel cell, hepatocellular, MSI-high colorectal and esophageal squamous cancers and melanoma in partial response, with immunotherapy alone or in combination, the protocol says. The rationale was that responses can persist after treatment stops and that pharmacokinetic studies show no clear dose effect, so less frequent dosing might reduce toxicity and cost. The primary endpoint was progression-free survival, with a noninferiority margin of a hazard ratio of 1.30 (NCT05078047).
What happened?
The trial randomized 340 patients across 36 centers, 171 to standard dosing and 169 to every 12 weeks, before it was stopped for an overall survival imbalance favoring standard dosing. In the modified intention-to-treat population, median progression-free survival was 25.0 months with standard dosing versus 21.9 months with reduced dosing (HR 1.35; 96.16% CI, 0.90 to 2.04), so noninferiority was not shown. Deaths occurred in 10.5 percent of the standard arm and 19.9 percent of the reduced arm, Targeted Oncology reported, for an overall survival hazard ratio of about 2 (2.04; 95% CI, 1.08 to 3.85). The randomized-and-treated population showed the same pattern (overall survival HR 1.89). Subgroup estimates were imprecise, with the worst progression-free survival signal in urothelial cancer (HR 2.9), OncoDaily reported.
Reduced dosing did not buy a safety advantage. Grade 3 or 4 adverse events occurred in 29.8 percent with standard dosing and 34.5 percent with reduced dosing, and grade 3 or 4 treatment-related events in 10.5 versus 9.5 percent.
Fewer infusions sounded like a free win for responding patients. In MOIO, the reduced schedule did not lower serious toxicity, and more patients died.
How to read the result
By The Script Pad's arithmetic, MOIO enrolled 340 of its 646 planned patients, about 53 percent, and the death rate in the reduced arm was about 1.9 times that of the standard arm, roughly nine more deaths per 100 patients at a median follow-up of 18.6 months. Early stopping and a mixed-tumor population mean the true size of the harm is uncertain, and the confidence interval is wide. The direction is not uncertain enough to justify the strategy outside a trial.
What it means in clinic
Ad hoc stretching of checkpoint inhibitor intervals for responders, whether for convenience, cost or patient preference, now has phase 3 evidence against it. Labeled extended-interval schedules, such as the every-six-week pembrolizumab dosing used in recent trials, are a different question that MOIO did not test, and stopping treatment altogether at a planned time was not studied here. When patients ask for fewer visits, the conversation should include this result, framed in absolute terms as described in our guide to communicating risk. For other immunotherapy data from the same congress, see INTerpath-001 in melanoma.
Reported, fact-checked and edited by The Script Pad's editorial staff. See How we use AI.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
