Abstract 670P
Background
Discordant radiographic responses are described in other tumor types in response to immunotherapy with response at some anatomic sites and progression in others. Here we determined the frequency of discordant pathologic tumor response (pTR) in HNSCC patients treated with ICI in the context of neoadjuvant trials.
Methods
We conducted two multi-institutional, neoadjuvant immunotherapy trials in patients with previously untreated HNSCC of any stage who were candidates for complete surgical resection. Patients were stratified by HPV status. Trials analyzed utilized nivolumab as the PD-1 inhibitor with randomization to the IDO inhibitor (BMS986205) in one trial and tadalafil in the second trial. Resection specimens were graded by two pathologists. Areas exhibiting pTR, defined by fibrosis with chronic inflammation, foamy macrophage reaction and multinucleated giant cells, were expressed relative to the total tumor area. pTR was assessed in the primary tumor and all lymph nodes (LN). Discordance was defined as two sites of disease having >=25% difference in the pTR value assigned.
Results
24/46 (52%) of subjects experienced concordant pTR in the primary tumor and LNs. This includes 3 complete pathologic responses. In contrast, 22/46 patients (48%) revealed discordant pTR between the primary tumor sites (average of 17% TE) and involved LNs (average of 62% TE) (p= 0.018; signed rank test). Interestingly, in the discordant group, pTR effects in LNs were invariably greater than in primary lesions. In 9/21 patients with multiple involved LN, the pTR varied between these nodes significantly. This included patients with adjacent LNs demonstrating 0% and 100% pTR in the same level. HPV status was not significantly associated with discordant pTR. Systemic and local immune profiles as they relate to concordant and discordant pTR in individual patients will be presented.
Conclusions
pTR in patients with previously untreated HNSCC receiving neoadjuvant ICI demonstrate a wide variety of response between the primary tumor and regional lymph nodes within the same patient. The clinical implication of discordant responses remain to be defined as we investigate the use of neoadjuvant ICI.
Clinical trial identification
NCT03238365, NCT03854032.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bristol Myers Squibb.
Disclosure
All authors have declared no conflicts of interest.