Manushak Avagyan, Associate Medical Director at Agenus, shared on LinkedIn:
“‘Neoadjuvant immunotherapy is here to stay.’
That line from Dr. G. Paul Wright sums up yesterday’s Society for Immunotherapy of Cancer (SITC) Advances in Cancer Immunotherapy (ACI): A Focus on Neoadjuvant Immunotherapy.
The two closing talks tied everything together for me.
- Dr. Wright gave the surgeon’s view, reassuring but practical. In the melanoma trials, roughly 9 in 10 patients still made it to surgery, and when they didn’t, progression was a bigger reason than toxicity. IO is non-cytotoxic, so it doesn’t impair wound healing. But irAEs belong in the surgical and anesthesia plan, from pneumonitis and the airway to adrenal insufficiency, and postoperative colitis and sepsis can look alike. Imaging doesn’t always tell us who truly responded.
- Dr. James Larkin reframed the question we keep asking: what a drug adds is different from what timing adds. We need standardized pathologic response, a clear link to EFS and OS, and rigorous trials that isolate the contribution of each phase. There is no ‘one size fits all.’
Melanoma shows why this matters. Dr. Leslie Fecher walked through the experience, and the S1801 design is elegant: 3 cycles of pembrolizumab before surgery and 15 after, versus 18 all after. Same drug, same total cycles, only the timing changed, and outcomes improved. NADINA then let pathologic response guide what comes next. The tumor becomes a readout, not just a target.
Why neoadjuvant works (Drs. Larkin and Fecher):
- Treating with the tumor in place may drive stronger T-cell priming
- Pathologic response is an early signal and a biomarker platform
- Downstaging can make surgery less morbid
- Response can help us de-escalate, or escalate, adjuvant therapy
Beyond melanoma: in MSI-high colorectal cancer, Dr. Yelena Janjigian showed striking early activity with one preoperative cycle of botensilimab + balstilimab (UNICORN). What I find equally exciting is that the same combination is also showing early signals in MSS disease, long considered IO-resistant. The data are small, but they raise the right question: how much therapy do we need, and for whom?
Thank you to Drs. Wright, Larkin, Fecher, and Janjigian for such fulfilling lectures, to Drs. Uppaluri, Bex, Kok, and Owen, and to SITC for a rich program.
I’m launching Peri-IO Safety, a new SITC Special Interest Group on Perioperative Immunotherapy Safety and Toxicity. If you work on neoadjuvant or adjuvant IO in clinical care, surgery, pathology, or research, I’d love to have you involved.”
Society for Immunotherapy of Cancer (SITC) added:
“Thanks Dr. Manushak Avagyan for your thoughtful analysis of yesterdays ACI. We appreciate your involvement!”
You may also be interested in: Tumor Mutational Burden Predicts Response to Neoadjuvant Immunotherapy
