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

Seiwert, Tanguy Y.; Foster, Corey C.; Blair, Elizabeth A.; Karrison, Theodore; Agrawal, Nishant; Melotek, J.M.; Portugal, Louis; Brisson, Ryan J.; Dekker, A.; Kochanny, Sara; Gooi, Zhen; Lingen, Mark W.; Villaflor, Victoria M.; Ginat, Daniel Thomas; Haraf, D. J.; Vokes, Everett E.

doi:10.1093/annonc/mdz171

Cited by 44 publications

(61 citation statements)

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“…The OPTIMA trial did look at surgical pathology following induction chemotherapy and the dose reduced radiation, but all patients received both induction chemotherapy and radiation therapy (50 and 45 Gy) prior to surgical resection. 13 Therefore, their finding of pCR of 92% is promising for de-escalation but not comparable to the findings in our study. 13 The controversy on use of neoadjuvant chemotherapy has risen with its use in the context of heterogeneous group of head and neck cancer patients including many sites and p16 negative as well as p16 positive tumors, all with differing behavior (DeCIDE study).…”

Section: Discussioncontrasting

confidence: 96%

“…13 Therefore, their finding of pCR of 92% is promising for de-escalation but not comparable to the findings in our study. 13 The controversy on use of neoadjuvant chemotherapy has risen with its use in the context of heterogeneous group of head and neck cancer patients including many sites and p16 negative as well as p16 positive tumors, all with differing behavior (DeCIDE study). [14][15][16] It is further complicated by its use in combination with aggressive and toxic CCRT resulting in treatment fallouts and significant treatment-related mortality in neoadjuvant chemotherapy arm.…”

Section: Discussioncontrasting

confidence: 96%

“…4 Several studies have also looked at the use of induction chemotherapy in HPV-associated OPC in order to select the good-responders as candidates for radiation dose reduction protocols. 1,7,12,13 In addition to using induction chemotherapy as a predictor of radioresponsiveness, its use allows for tumor size reduction and a proposed requirement for lower dose of radiation therapy to treat the resulting subclinical tumor. 1,12 This concept of responsiveness and tumor size reduction is similar in the current study.…”

Section: Discussionmentioning

confidence: 99%

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Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

et al. 2019

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Background: A paradigm shift has led to de-escalation trials for the treatment of HPV-positive oropharynx cancer (OPC). The objective of this study was to assess the ability of tumor volume reduction on imaging to predict pathological response to neoadjuvant chemotherapy in patients with HPV-positive OPC.Methods: A prospective observational study of 54 patients with HPV-positive OPC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. Patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); prechemotherapy and postchemotherapy imaging were obtained. Receiver operating characteristic curves and logistic regression analyses were used. Results: The complete pathologic response (pCR) rate at primary and nodal sites were 72% and 57%, respectively. Tumor volume reduction of ≥90% following induction chemotherapy predicted pCR of the primary tumor. Conclusions: Neoadjuvant chemotherapy followed by definitive transoral surgery is a new paradigm worthy of further investigation and MRI is a reliable modality to assess preoperative response.

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Section: Discussioncontrasting

confidence: 96%

Section: Discussioncontrasting

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

et al. 2019

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“…5 Although the prognostic value of HPV status in OPSCC has been established, the predictive capacity of HPV is less clear. 3,6,7 The standard of care for nonsurgical treatment of OPSCC remains chemoradiation. 1 Conventionally, (RT) is delivered using an intensity-modulated radiotherapy (IMRT) technique concurrently with high-dose platinum-based chemotherapy to a gross tumor dose of 66 to 70 Gy.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] Considering the favorable prognostic value of HPV+ OPSCC, 3 several trials are underway to examine the role of radiotherapeutic dose reduction in an effort to reduce treatment-related morbidity. 6,[12][13][14][15][16] Owing to the high level of interest in de-escalating RT dose, we sought to compare national trends thereof, as well as compare outcomes in patients receiving conventional and de-escalated radiation doses with and without HPV-mediated disease.…”

Section: Introductionmentioning

confidence: 99%

Practice patterns and outcomes following radiation dose de‐escalation for oropharyngeal cancer

et al. 2019

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Objectives/Hypothesis Numerous trials are evaluating radiotherapy (RT) de‐escalation for human papillomavirus (HPV)‐mediated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Herein, we evaluated the degree to which de‐escalated RT is delivered in the United States, as well as comparative outcomes with full‐dose RT as stratified for HPV status. Study Design Retrospective database review. Methods We identified patients diagnosed with OPSCC in the National Cancer Database, excluding those with stage I/II disease, unknown HPV status, receiving surgery or not receiving external beam radiation therapy to the primary site, receipt of radiation doses >75 or <54 Gy, radiation treatment course duration <25 or >75 days, and unknown or inadequate (<2 months) follow‐up. Multivariable logistic regression analysis identified variables associated with delivery of de‐escalated RT (<66 Gy). Overall survival of HPV+ and non–HPV‐mediated (HPV−) disease was compared between full‐dose and de‐escalated approaches. Results Altogether, 617 and 551 patients were HPV+ and HPV−, respectively. De‐escalated RT was delivered in 16.9% HPV+ and 15.2% of HPV− disease, respectively. Older patients and omission of systemic therapy were more likely to receive de‐escalated RT. In HPV+ patients, 3‐ and 5‐year survival rates were 83% and 80% in the de‐escalated cohort versus 83% and 78% in the full‐dose group (P = .83). In HPV− patients, corresponding 3‐ and 5‐year survival rates were 29% and 23% versus 61% and 51% (P = .001). Conclusions National utilization of de‐escalated RT for OPSCC is low (15%–20%), but does not seem to impact overall survival in HPV+ (but not HPV−) patients. The caveats of this heterogeneous, retrospective analysis require corroboration from a number of ongoing randomized trials. Level of Evidence 2c Laryngoscope, 130:E171–E176, 2020

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Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV⁺ Oropharyngeal Cancer

Rosenberg,

Agrawal,

Juloori

et al. 2024

JAMA Oncol

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ImportanceImmune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus−positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity.ObjectiveTo determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC.Design, Setting, and ParticipantsThis phase 2 nonrandomized clinical trial conducted at a single academic center enrolled 77 patients with locoregionally advanced HPV+ OPC from 2017 to 2020. Data analyses were performed from February 10, 2021, to January 9, 2023.InterventionsAddition of nivolumab to neoadjuvant nab-paclitaxel and carboplatin (studied in the first OPTIMA trial) followed by response-adapted LRT in patients with HPV+ OPC stages III to IV.Main Outcomes and MeasuresPrimary outcome was deep response rate to neoadjuvant nivolumab plus chemotherapy, defined as the proportion of tumors with 50% or greater shrinkage per the Response Evaluation Criteria in Solid Tumors 1.1. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). Swallowing function, quality of life, and tissue- and blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression and circulating tumor HPV-DNA (ctHPV-DNA), were also evaluated.ResultsThe 73 eligible patients (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started neoadjuvant nivolumab and chemotherapy. Deep responses were observed in 51 patients (70.8%; 95% CI, 0.59-0.81). Subsequent risk- and response-adaptive therapy was assigned as follows: group A, single-modality radiotherapy alone or transoral robotic surgery (28 patients); group B, intermediate-dose chemoradiotherapy of 45 to 50 Gray (34 patients); and group C, regular-dose chemoradiotherapy of 70 to 75 Gray (10 patients). Two-year PFS and OS were 90.0% (95% CI, 0.80-0.95) and 91.4% (95% CI, 0.82-0.96), respectively. By response-adapted group, 2-year PFS and OS for group A were 96.4% and 96.4%, and group B, 88.0% and 91.0%, respectively. Lower enteral feeding rates and changes in weight, as well as improved swallowing, were observed among patients who received response-adapted LRT. Pathologic complete response rate among patients who underwent transoral robotic surgery was 67.0%. PD-L1 expression was nonsignificantly higher for deeper responses and improved PFS, and ctHPV-DNA clearance was significantly associated with improved PFS.Conclusions and RelevanceThis phase 2 nonrandomized clinical trial found that neoadjuvant nivolumab and chemotherapy followed by response-adapted LRT is feasible and has favorable tolerability, excellent OS, and improved functional outcomes in HPV+ OPC, including among patients with high-risk disease. Moreover, addition of nivolumab may benefit high PD-L1 expressors, and sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful for patient selection.Trial RegistrationClinicalTrials.gov Identifier: NCT03107182

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

Cited by 44 publications

References 0 publications

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

Practice patterns and outcomes following radiation dose de‐escalation for oropharyngeal cancer

Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV⁺ Oropharyngeal Cancer

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

Cited by 44 publications

References 0 publications

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

Pathologic response to neoadjuvant chemotherapy in HPV‐associated oropharynx cancer

Practice patterns and outcomes following radiation dose de‐escalation for oropharyngeal cancer

Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer

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Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV⁺ Oropharyngeal Cancer