Definitive Chemoradiation with Concurrent Carboplatin and Paclitaxel for HPV-Mediated Oropharyngeal Cancer (p16+ OPSCC): Survival and Local Control

Abstract

Standard therapy for locally advanced p16+ OPSCC with cisplatin and bilateral nodal RT results in substantial acute and late toxicities. De-intensification strategies are under active investigation, including the de-escalation of RT dose and field size and use of less toxic RT sensitizing agents. We present our single-institution experience with definitive chemoRT using weekly carboplatin and paclitaxel and modified RT. A retrospective review of 139 consecutive patients with non-metastatic p16+ OPSCC treated with definitive chemoRT from 2013 to 2019 was performed. IMRT dose ranged from 60 to 70 Gy (median 69.96 Gy) to gross disease and 44 to 59.4 Gy (median 54.45 Gy) to elective nodal sites. Modified RT included dose reduction from 70 Gy EQD2 to 60-67.8 Gy EQD2 (2.0-2.2 Gy/fraction) and/or field modified contralateral neck. All patients received concurrent weekly paclitaxel (30 mg/m2) and carboplatin (AUC 1); 34 (24.5%) received induction chemotherapy. Patients were classified as low or intermediate risk based on HPV status, smoking history, and nodal staging per RTOG 0129 risk stratification. OS, local and regional RFS, and DSS were estimated using Kaplan-Meier method. Median FU was 40.5 months. Of 139 pts, 96 were low and 43 were intermediate risk. Median age 61 yrs (range, 40-81 yrs). 125 pts were male and 14 were female. TNM staging: 29 pts (20.9%) were T1 (22 N1, 7 N2), 68 (48.9%) T2 (4 N0, 52 N1, 12 N2), 27 (19.4%) T3 (5 N0, 15 N1, 7 N2), and 15 (10.8%) T4 (2 N0, 2 N1, 10 N2, 1 N3). Median smoking history of 22.5 pack-yrs (range, 0.25-150 pack-yrs); 59 never smoked. LR recurrence was noted in 6/96 (6.3%) low risk and 7/43 (16.3%) intermediate risk pts. DM developed in 11/96 (11.5%) low risk and 8/43 (18.6%) intermediate risk pts. Synchronous LR recurrence and DM were noted in 1/96 (1%) low risk and 2/43 (4.7%) intermediate risk pts. The 3-year LRC was 93.6% (95% CI, 86.3-97.1) in the low-risk and 77.8% (95% CI, 61.4-87.8) in the intermediate-risk group. The 3-year OS was 95.4% (95% CI, 88.3-98.3) in the low-risk and 77.6% (95% CI, 61.3 to 87.7) in the intermediate-risk group. The 3-year DSS was 96.6% (95% CI, 89.7-98.9) in the low-risk and 86.8% (95% CI, 71.0-94.3) in the intermediate-risk group. Definitive chemoRT for p16+ OPSCC with concurrent carboplatin and paclitaxel and a modified RT regimen designed to minimize acute and late effects of therapy demonstrated comparable outcomes to standard cisplatin-based chemoRT, such as report on RTOG 0129, with a high rate of LRC at 3 years. Our analysis suggests a role for a less intensive regimen using paclitaxel and carboplatin as a less toxic, effective alternative to cisplatin in the curative management of p16+ OPSCC, particularly in low-risk patients. Strategies for combating distant metastases are needed. Toxicity analysis planned to be presented separately.