OncLive: In the first portion of our interview, you mentioned an age imbalance between the trial arms. What should be known about that as it relates to the sensitivity analyses performed in the trial?
ADAM Trial: Next Steps and Broader Significance in Merkel Cell Carcinoma
- Sensitivity analyses adjusting for baseline imbalances between arms did not qualitatively change the ADAM trial’s results (unadjusted stratified HR for RFS, approximately 0.6).
- Data from the randomized ADAM trial are the first prospective findings in patients with high-risk stage III Merkel cell carcinoma, distinguishing it from prior adjuvant studies conducted in lower-risk disease.
- Investigators are also presenting separate data suggesting that the timing of immunotherapy infusions does not meaningfully affect outcomes, a question of growing interest given data in other tumor types.
Bhatia: We did have a prespecified adjustment for confounding variables built into our protocol, and we did that. Age was the only variable that was statistically different between the 2 groups. Numerically, the avelumab group also had a higher proportion of [males], which is also associated with poorer outcomes, and somewhat higher ECOG scores. We did sensitivity analyses adjusting for those, and [none] of those qualitatively changed our results. Even if you don’t adjust for it, the stratified HR is around 0.6, which is still impressive compared with many other adjuvant settings.
What is the significance of the ADAM trial data?
Dissemination of these data is going to be important. It will be interesting to see how the scientific community reacts to these data, but my hope is that [they] will guide the discussions for many years to come, and not just in the clinic, but also on the research side…. Hopefully, these data are going to guide the future generation of trials while [they] inform us in the clinic.
What research findings presented at ASCO 2026 will be most significant in your field this year?
I would like to propose that our study is going to be informative. One thing that we are missing in most adjuvant and neoadjuvant trial discussions is [that] we are focusing on the short-term end points of [RFS], but as the MCC data point out, that does not necessarily mean we have to treat all our patients with adjuvant therapy. We need to strive for longer-term survival benefit when it comes to adjuvant therapy.
The other thing I would like to highlight is [that] we are also presenting an abstract on the timing of immunotherapy infusions, which has been a hot area lately; a lot of studies have pointed out that morning or early infusions of immunotherapy might have better outcomes, which a lot of clinics are now even thinking about adopting, which poses huge logistical challenges. We looked at that data at our center; we have been using immunotherapy for 15-plus years, and we basically see no difference in outcomes based on the timing of immunotherapy infusions, which makes intuitive sense based on the mechanism of action of these drugs and also the fact that these antibodies last in the serum for months after administration. I’m hoping we will stir [up] some more conversation in that controversial field.
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
References
- Bhatia S, Gooley T, Brohl AS, et al. ADAM trial: a multicenter, randomized, double-blinded, placebo-controlled, phase 3 trial of adjuvant avelumab (anti-PD-L1 antibody) in patients with Merkel cell carcinoma and lymph node metastases. J Clin Oncol. 2026;44(suppl 17):LBA9504. doi:10.1200/JCO.2026.44.17_suppl.LBA9504
- McEvoy AM, Lachance K, Hippe DS, et al. Recurrence and mortality risk of Merkel cell carcinoma by cancer stage and time from diagnosis. JAMA Dermatol. 2022;158(4):382-389. doi:10.1001/jamadermatol.2021.6096
