Ralph Zinner, MD University of Kentucky discusses an ASCO 2020 abstract entitled Neoadjuvant nivolumab (N) plus weekly carboplatin (C) and paclitaxel (P) in resectable locally advanced head and neck cancer

Bottom line:
Patients (pts) with resectable locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) are at high risk for recurrence, despite normal multimodality treatment. Improved overall survival of pts with pathologic complete response (pCR) or significant pathologic response (MPR) to neoadjuvant chemotherapy. In conjunction with platinum-based chemotherapy, PD-1 checkpoint inhibitors are approved for 1st-line treatment of recurrent / metastatic SCCHN. We believe that, relative to historical controls, the addition of N to wkly carboplatin C and P would increase the pCR rate at the primary site.

Approaches:
This is an investigator-initiated study for HPV-(oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L) or stage II-III HPV+ OP SCCHN pts with newly diagnosed (AJCC 8th) stage III-IV without distant metastases that are surgical candidates. 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 with wk 8 surgery. At the primary site the primary endpoint is pCR. The resected pathology specimens are cut > 1 segment / cm to estimate pathological response. Slides are imaged and then annotated by at least 2 pathologists using the Aperio Automated scanning method for viable tumor vs. treatment results, with areas automatically measured to yield the percentage of viable tumor. Our primary endpoint is reached if the expected 11/37 pts have a pCR at the primary site.

Reviews:
From 11/17-12/19, 27 pts got the study regimen and underwent surgery (1/27 had a primary unknown; thus, unavoidable for the primary endpoint). The median age of 27 pts was 59 (46-83), females 31 percent, HPV+ 15 percent, OC 73 percent, OP 19 percent, HP 7 percent, L 4 percent; stage III 33 percent, stage IVA 67 percent. The toxicity of Gd 3 was 37% pts; 1 pt febrile neutropenia, 3 pts anemia, 1 pt diarrhea, 1 pt cellulitis and 1 pt rash. Four pts have had neutropenia of gd 3-4. The dose reduction was in 2 pts, and 4 pts had dropped 1 wkly dose. All 27 pts went to surgery; all with negative margins, none with PD by CT. With rapid recurrence, one pt died; no more recurrences (median f / u 13 mos). Our primary endpoint was met; at the primary site there was a pCR of 11/26 (42 per cent) pts (excluding pt with unknown primary). HPV-pts 9/23 (39 percent), had a pCR. MPR or pCR was 18/26 (69 percent) and 15/23 (65 percent) in HPV- pts. 2/11 pts each had a residual microscopic disease at 1 LN.

Findings:
N and wkly PC combined was well tolerated. The primary endpoint of pCR > 11/37 pts at the primary site was reached by the 27th pt. Continues with Accrual. Exploratory results are under way to test indicators of immune bias in tumor tissue and plasma. Data on clinical trials: NCT03342911.