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Clinical Trial
. 2021 Nov:122:105566.
doi: 10.1016/j.oraloncology.2021.105566. Epub 2021 Oct 18.

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience

Ari J Rosenberg  1 , Nishant Agrawal  2 , Alexander Pearson  3 , Zhen Gooi  2 , Elizabeth Blair  2 , John Cursio  4 , Aditya Juloori  5 , Daniel Ginat  6 , Adam Howard  2 , Jeffrey Chin  3 , Sara Kochanny  3 , Corey Foster  7 , Nicole Cipriani  8 , Mark Lingen  8 , Evgeny Izumchenko  3 , Tanguy Y Seiwert  9 , Daniel Haraf  5 , Everett E Vokes  3
Affiliations
Clinical Trial

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience

Ari J Rosenberg et al. Oral Oncol. 2021 Nov.

Abstract

Background: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC.

Methods: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30-50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75).

Results: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05).

Conclusion: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.

Keywords: Chemotherapy; Head and neck cancer; Human papillomavirus; Radiation therapy; Treatment de-intensification.

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Conflict of interest statement

Authors’ disclosures of potential conflicts of interest:

Conflict of Interest Statement:

ZG, EB, JC, DG, AH, JC, SK, CF, NC, ML, EI, and DH report no conflicts of interest.

Figures

Figure 1:
Figure 1:
OPTIMA paradigm treatment schema for (A) low risk and (B) high risk.
Figure 2:
Figure 2:
Consort diagram with flow of patients treated per OPTIMA paradigm.
Figure 3:
Figure 3:
Overall survival for (A) All patients treated, (B) Stratified by high risk and low risk patients, and (C) Stratified by treatment group with RT50, CRT45, or CRT75.
Figure 3:
Figure 3:
Overall survival for (A) All patients treated, (B) Stratified by high risk and low risk patients, and (C) Stratified by treatment group with RT50, CRT45, or CRT75.
Figure 4:
Figure 4:
Progression free survival for (A) All patients treated, (B) Stratified by high risk and low risk patients, and (C) Stratified by treatment group with RT50, CRT45, or CRT75.
Figure 4:
Figure 4:
Progression free survival for (A) All patients treated, (B) Stratified by high risk and low risk patients, and (C) Stratified by treatment group with RT50, CRT45, or CRT75.
Figure 5:
Figure 5:
Enteral feeding dependency from the end of (chemo)radiation by treatment arm.
See this image and copyright information in PMC

References

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