Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

T. Y. Seiwert; C. C. Foster; E. A. Blair; T. G. Karrison; N. Agrawal; J. M. Melotek; L. Portugal; R. J. Brisson; A. Dekker; S. Kochanny; Z. Gooi; M. W. Lingen; V. M. Villaflor; D. T. Ginat; D. J. Haraf; E. E. Vokes

doi:10.1093/annonc/mdy522

Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

T. Y. Seiwert, C. C. Foster, E. A. Blair, T. G. Karrison, N. Agrawal, J. M. Melotek, L. Portugal, R. J. Brisson, A. Dekker, S. Kochanny, Z. Gooi, M. W. Lingen, V. M. Villaflor, D. T. Ginat, D. J. Haraf, E. E. Vokes^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

108 Scopus citations

Abstract

Background Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. Patients and methods Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration Clinical trials.gov identifier: NCT02258659.

Original language	English (US)
Pages (from-to)	297-302
Number of pages	6
Journal	Annals of Oncology
Volume	30
Issue number	2
DOIs	https://doi.org/10.1093/annonc/mdy522
State	Published - Feb 1 2019

Keywords

Chemoradiation
Human papillomavirus
Induction chemotherapy
Oropharyngeal cancer
Treatment de-escalation

ASJC Scopus subject areas

Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/annonc/mdy522

Cite this

Seiwert, T. Y., Foster, C. C., Blair, E. A., Karrison, T. G., Agrawal, N., Melotek, J. M., Portugal, L., Brisson, R. J., Dekker, A., Kochanny, S., Gooi, Z., Lingen, M. W., Villaflor, V. M., Ginat, D. T., Haraf, D. J., & Vokes, E. E. (2019). Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Annals of Oncology, 30(2), 297-302. https://doi.org/10.1093/annonc/mdy522

@article{c1e6b1245a6d472d90278b5449e95509,

title = "Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer",

abstract = "Background Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. Patients and methods Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration Clinical trials.gov identifier: NCT02258659.",

keywords = "Chemoradiation, Human papillomavirus, Induction chemotherapy, Oropharyngeal cancer, Treatment de-escalation",

author = "Seiwert, {T. Y.} and Foster, {C. C.} and Blair, {E. A.} and Karrison, {T. G.} and N. Agrawal and Melotek, {J. M.} and L. Portugal and Brisson, {R. J.} and A. Dekker and S. Kochanny and Z. Gooi and Lingen, {M. W.} and Villaflor, {V. M.} and Ginat, {D. T.} and Haraf, {D. J.} and Vokes, {E. E.}",

note = "Funding Information: This work was supported by Celgene. No grant number applicable. Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.",

year = "2019",

month = feb,

day = "1",

doi = "10.1093/annonc/mdy522",

language = "English (US)",

volume = "30",

pages = "297--302",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "2",

}

Seiwert, TY, Foster, CC, Blair, EA, Karrison, TG, Agrawal, N, Melotek, JM, Portugal, L, Brisson, RJ, Dekker, A, Kochanny, S, Gooi, Z, Lingen, MW, Villaflor, VM, Ginat, DT, Haraf, DJ & Vokes, EE 2019, 'Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer', Annals of Oncology, vol. 30, no. 2, pp. 297-302. https://doi.org/10.1093/annonc/mdy522

TY - JOUR

T1 - Optima

T2 - A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

AU - Seiwert, T. Y.

AU - Foster, C. C.

AU - Blair, E. A.

AU - Karrison, T. G.

AU - Agrawal, N.

AU - Melotek, J. M.

AU - Portugal, L.

AU - Brisson, R. J.

AU - Dekker, A.

AU - Kochanny, S.

AU - Gooi, Z.

AU - Lingen, M. W.

AU - Villaflor, V. M.

AU - Ginat, D. T.

AU - Haraf, D. J.

AU - Vokes, E. E.

N1 - Funding Information: This work was supported by Celgene. No grant number applicable. Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Background Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. Patients and methods Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration Clinical trials.gov identifier: NCT02258659.

AB - Background Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy. Patients and methods Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity. Results Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001). Conclusions Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified. Clinical trial registration Clinical trials.gov identifier: NCT02258659.

KW - Chemoradiation

KW - Human papillomavirus

KW - Induction chemotherapy

KW - Oropharyngeal cancer

KW - Treatment de-escalation

UR - http://www.scopus.com/inward/record.url?scp=85061969703&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061969703&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdy522

DO - 10.1093/annonc/mdy522

M3 - Article

C2 - 30481287

AN - SCOPUS:85061969703

SN - 0923-7534

VL - 30

SP - 297

EP - 302

JO - Annals of Oncology

JF - Annals of Oncology

IS - 2

ER -

Optima: A phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this