ESMO 2025 | Assessing rates of attrition to surgery for lung cancer

Any time we give neoadjuvant or perioperative approach, there is, you know, in Checkmate 816, it was up to three cycles of chemo and neo. In the perioperative trials, it was upwards up to four cycles. So there is an inherent delay to getting that patient to surgery. And there’s an inherent attrition to surgery. And that attrition rates are roughly about 20% of patients that don’t make it to surgery. But when we look at phase three randomized trials, and the only one I know of that looked at head-to-head, upfront surgery alone, upfront surgery, then adjuvant chemo, or neoadjuvant chemo, then go to surgery. And this is before the era of targeted therapies in IO, and that’s the NATCH trial and the Spanish lung cancer group trial. And in that study, they looked at, one of the things they looked at was attrition to surgery. And across the board, regardless of the intent to treat, there was about a 9% attrition in all three arms. So we don’t talk about attrition to surgery in the adjuvant IO trials. And there’s been three IO adjuvant trials in early stage lung cancer, which have included IMpower010, KEYNOTE-091, and then BR31. And all three of them, the randomization was following complete resection. And because of the trial design, we don’t talk about attrition to surgery in the adjuvant trials, but they clearly exist when you look at like the NACH trial. And so I think the attrition rates are probably overestimates of what the real attrition rates are from the neoadjuvant approach because there’s an inherent baseline attrition regardless of your intent to treat. The latest surgery is a little arbitrary in the sense that the protocol defines a window for surgery. And in most of the phase three registrational trials in the early stage setting, it was at six weeks, roughly six weeks. AEGEAN had the shortest at 5.7 weeks. And all the other trials were at six weeks to go to surgery, and KEYNOTE-671was at eight weeks. So the rates are variable because the protocol defines a window differently. But most patients make it to surgery, and there was no difference when they controlled chemotherapy alone harm. So I think the surgical delays and the attrition rates are acceptable rates. When you look at progression of disease and adverse events that have prevented patients from going to surgery or delayed the surgery, those numbers are in the low single digits. So for the most part, AEs and progression of disease account for a small minority of patients when you look at the total cohort altogether. So I think overall it’s safe, and I think those are acceptable numbers for attrition and delays in surgery.

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