968P - Neoadjuvant nivolumab (N) plus weekly carboplatin (C) and paclitaxel (P) outcomes in HPV(-) resectable locally advanced head and neck cancer

Background

Patients (pts) with resectable locally advanced squamous cell carcinoma of the head and neck (SCCHN) have high risk for recurrence. Pts with pathologic complete response (pCR) or major pathologic response (MPR) to neoadjuvant chemo have improved overall survival. PD-1 checkpoint inhibitors are approved in combination with platinum-based chemo in 1st-line recurrent/metastatic SCCHN. We hypothesize adding N to wkly C and P will increase the pCR rate at the primary site.

Methods

This is an investigator-initiated trial in newly diagnosed surgical (AJCC 8^th) stage III-IV HPV(-) oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L) or stage II-III HPV(+) OP SCCHN without distant metastasis. D1 is C AUC 2 IV wkly x 6 plus P 100 mg/m2 IV wkly x 6 plus N 240 mg IV q 2 wks x 3; surgery on wk 8. The primary endpoint is pCR at the primary site. Specimens are cut >1 section/cm. Using the Aperio Digital scanning system©, slides are imaged, and annotated by ≥ 2 pathologists for viable tumor vs. treatment effect with calculated % of viable tumor. Our primary endpoint will be reached if 11/37 planned pts have a pCR at the primary site. The analysis here is in the HPV(-) pts.

Results

From 11/2017-5/2020, 32 pts had treatment on the study regimen followed by surgery of whom 26 were either HPV(-) (24 pts) or HPV unknown but who had OC (2 pts). Of these 26 pts, median age was 59 (46-83), women 35%, OC 81%, OP 12%, HP 4%, L 4%; stage III 23%, stage IVA 77%. Gd 3 or 4 toxicities were in 9/26 (35%) pts, 1 pt gd 3 febrile neutropenia, 3pts gd 3 anemia, 1pt gd 3 diarrhea, 1pt gd 3 cellulitis, 1 pt gd 3 muscle weakness, 1 pt gd 3 rash, and 4 pts gd 3-4 neutropenia. Dose reductions were in 2 pts, and 3 pts had 1 wkly dose dropped. No pts had PD by CT; all had negative margins at surgery. Our primary endpoint was met even when excluding HPV(+) pts; 11/26 (42%) pts had a pCR at the primary site. 2/11 of these pts had microscopic residual disease outside the primary site, 1 LN each. MPR or pCR was 17/26 (65%).

Conclusions

The combination of N and wkly PC was well tolerated. The primary endpoint of pCR at the primary site in ≥ 11/37 pts was met even when excluding HPV(+) pts. Confirmatory trials are being considered.

Clinical trial identification

NCT03342911.

Editorial acknowledgement

Legal entity responsible for the study

Thomas Jefferson University Hospital.

Funding

Bristol-Myers Squibb.

Disclosure

All authors have declared no conflicts of interest.