Imagine challenging the status quo in cancer care: what if we could prove that dialing back on treatment intensity actually works just as well – or even better – without the massive hurdles of traditional studies? That’s the game-changing perspective from oncology expert Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, an Associate Professor of Medical Oncology at Leiden University Medical Center. In a recent LinkedIn update (check it out here: https://www.linkedin.com/posts/sahar-barjesteh-van-waalwijk-van-doorn-khosrovani-30ba9433sonia-deescalation-cmf-activity-7394267749541163008-Wkec?utmsource=share&utmmedium=memberdesktop&rcm=ACoAAE0lFWsB8d0LgQ138oau2MrzyuaZUepMAmo), she spotlights a compelling paper by Bishal Gyawali, published in the prestigious JNCI: Journal of the National Cancer Institute.
Sahar dives right into a common frustration in oncology: for countless therapies, we simply don’t have solid data on the ideal dose or how long treatment should last. Typically, to demonstrate that a reduced dose or shorter course is ‘nearly as effective,’ researchers launch enormous, costly trials. These studies aim to define what ‘nearly as good’ truly entails – often using a statistical tool called a non-inferiority margin. But by the time results roll in, debates rage over that margin, and due to understandable caution around patient risks, many clinicians hesitate to adopt the less-intensive option. It’s a system that feels stuck, right?
But here’s where it gets intriguing – and potentially revolutionary: why not turn the question upside down? Instead of asking if less treatment measures up to the full regimen, ask whether the current heavy-duty standard is truly superior to a lighter approach. This shift places the onus of proof squarely on justifying more treatment, which, surprisingly, requires a smaller-scale study. It’s cheaper, quicker, and far more straightforward to execute. For beginners in clinical research, think of it like this: superiority trials test if one option beats another outright, while non-inferiority trials just check if it’s not much worse. Flipping to superiority for de-escalation could streamline things dramatically, avoiding those endless margin arguments.
Sahar urges readers to explore Bishal Gyawali’s fresh publication, which spotlights examples like the SONIA trial. Titled ‘De-escalation trials do not always need to be non-inferiority: A case for superiority design de-escalation trials in oncology,’ it makes a strong argument for this smarter trial design in cancer care. You can dive into the full article right here (https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djaf322/8315146?login=false).
She also points to related research on optimizing doses from Gauthier Bouche and colleagues (https://academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djaf322/8315146?login=false#google_vignette), plus an insightful piece titled ‘Less is more’ that echoes these themes (https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00532-2/fulltext). And this is the part most people miss: in a field where overtreatment can lead to unnecessary side effects and costs, embracing ‘less is more’ isn’t just efficient – it’s a potential ethical win for patients.
Author: Bishal Gyawali
For more from Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, explore these featured posts (https://oncodaily.com/tag/sahar-barjesteh-van-waalwijk-van-doorn-khosrovani). Credits go to Sahar Barjesteh van Waalwijk van Doorn-Khosrovani via LinkedIn and Bishal Gyawali via oncologybg.com.
Now, let’s stir the pot a bit: this superiority-flip idea boldly challenges the ingrained belief that more therapy always equals better outcomes, which could ruffle feathers among those wedded to aggressive standards. Is it time to rethink risk-aversion in oncology, or does this approach overlook hidden benefits of full dosing? What do you think – could superiority-designed de-escalation trials transform patient care, or are there pitfalls we’re not seeing? Drop your agreement, disagreements, or questions in the comments; I’d love to hear your take!