Abstract 2957
Background
The results of two consecutive phase II trials of patients with locally advanced HNSCC showed relapse rates of 13% after nab-paclitaxel, cisplatin, 5-FU and cetuximab (APFC) followed by CRT (Cancer 2013) and 3% after APF (no cetuximab) and CRT (Oral Oncology 2016). The complete response (CR) rates at the primary tumor site after 2 cycles of APFC was 53% and APF 77%. A comparison of APFC and CRT to APF and CRT showed no benefit of cetuximab (Oral Oncology 2017). In this phase II trial, we hypothesized similar efficacy with AP (no 5-FU) and CRT.
Methods
Eligibility criteria were similar to prior trials: stage III-IV oropharynx (OP), larynx, or hypopharynx SCC and adequate organ function and performance status (ECOG 0-1). T1 tumors were excluded. Treatment: 3 cycles of AP followed by CRT. AP: nab-paclitaxel 100 mg/m2 days 1,8 and 15 + cisplatin 75 mg/m2 day 1 in 3 week/cycles. CRT: Cisplatin 100 mg/m2 days 1, 22 and 43 or cetuximab weekly (if cisplatin-ineligible) and intensity modulated RT 70 Gy (200 cGy/day). The primary endpoint was clinical CR rate at the primary tumor site after 2 cycles of AP, determined by visual exam. With a non-inferiority margin of 19% (lower boundary: 58%), a 40 patient sample provided power = 0.80 at p = 0.05 to conclude the CR rate at the primary tumor site with AP was non-inferior to APF (77%).
Results
Characteristics of the 40 enrolled patients: mean age 57 years (range 42-77), smoker 68%, male 90%, and ECOG 0 (78%). Tumor characteristics: T3-4 (68%), > N2c (58%), and human papillomavirus (HPV)-related OPSCC (73%) or HPV-unrelated HNSCC (28%). CRT included cisplatin (36) or cetuximab (4). Clinical CR rate at the primary tumor site after 2 cycles AP was 70% (28 patients). Primary tumor site biopsies obtained following 2 cycles AP in 29 patients showed no cancer in 24 (83%). Post-cycle 2 biopsies showed no cancer in 19 of 20 evaluable patients with clinical CR. Median follow-up was 12.0 months (range: 0.1-19.6). Relapse rate was 8% (3 patients).
Conclusions
The CR rate at the primary tumor site after 2 cycles of AP was not inferior to that with APF. Deletion of 5-FU from APF did not reduce tumor response.
Clinical trial identification
NCT02573493.
Legal entity responsible for the study
Washington University School of Medicine.
Funding
Celgene.
Editorial Acknowledgement
Not Applicable.
Disclosure
D. Adkins: Advisory board: Pfizer, Merck; Research funding: Celgene, Pfizer, Merck, Novartis, Lilly, Gliknik, Astra Zeneca, MedImmune, Celldex, Chiltern, Blueprint Medicine. W. Thorstad: Spouse works for Elekta, Inc. All other authors have declared no conflicts of interest.