Non-Inferiority Margin and Nodal Analysis of De-Escalated Adjuvant Radiation Therapy (DART) for HPV-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Preplanned Pooled Analysis of MC1273 &amp; MC1675

Ma, Daniel; Price, Katharine A.; Moore, Eric J.; Patel, S.H.; Hinni, M.L.; Fruth, Briant; Foster, Nathan R.; Abel, K. Van; Yin, Linda X.; Neben-Wittich, M.A.; Garces, Y.; McGee, L.A.; Rwigema, J.C.; Routman, David M.; Lester, S.C.; Price, D.L.; Janus, Jeffrey R.; Chintakuntlawar, Ashish V.; Savvides, P.; Foote, Robert L.

doi:10.1016/j.ijrobp.2021.12.015

Cited by 5 publications

(5 citation statements)

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“…Again, progression was predominantly observed in patients who had AJCC Cancer Staging Manual , eighth edition (AJCC8) pN2 (>4 LNs) disease and ECE treated with DART, who experienced a 42.9% 2‐year PFS rate (vs. 100% with SOC); conclusions in patients who had pN2 disease without ECE cannot be drawn because only two such patients were enrolled. A preplanned pooled analysis of MC1273 and MC1675 reported a 2‐year PFS rate of 91.1% (95% CI, 87.2%–95.3%); this was both noninferior to the target 92.3% PFS for HN005 ( p = .29) and also higher than the HN005 acceptable PFS threshold of 86.9% ( p = .043) 61 . The ECE‐positive cohort did not achieve the target 92.3% or acceptable 86.9% PFS thresholds (85.2% and 78.6%, respectively), which were driven by failures in N2/ECE‐positive patients 61 .…”

Section: Surgical Deintensification Approaches Through Torsmentioning

confidence: 98%

“…A preplanned pooled analysis of MC1273 and MC1675 reported a 2‐year PFS rate of 91.1% (95% CI, 87.2%–95.3%); this was both noninferior to the target 92.3% PFS for HN005 ( p = .29) and also higher than the HN005 acceptable PFS threshold of 86.9% ( p = .043) 61 . The ECE‐positive cohort did not achieve the target 92.3% or acceptable 86.9% PFS thresholds (85.2% and 78.6%, respectively), which were driven by failures in N2/ECE‐positive patients 61 . A true noninferiority trial is estimated to require upward of 4000 patients to achieve a 1% noninferiority margin (more than all the TORS performed annually across all US academic centers), so these pooled results may be the best that can reasonably be achieved to address the question of DART after TORS.…”

Section: Surgical Deintensification Approaches Through Torsmentioning

confidence: 98%

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Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Kang

Chen

et al. 2022

CA A Cancer J Clinicians

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The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long‐term morbidities with chemoradiation and the favorable prognosis of HPV‐positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head‐and‐neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de‐escalation. National database studies estimate that up to one third of patients receive nonstandard de‐escalated treatments, which have subspecialty‐specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV‐positive OPC de‐escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de‐escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy‐based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de‐escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real‐time surveillance.

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Section: Surgical Deintensification Approaches Through Torsmentioning

confidence: 98%

Section: Surgical Deintensification Approaches Through Torsmentioning

confidence: 98%

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Kang

Chen

et al. 2022

CA A Cancer J Clinicians

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“…A preplanned pooled analysis of MC1273 and MC1675 reported 2-yr PFS of 91.1% (95% CI, 87.2%-95.3%), which is noninferior to the target PFS (92.3%, p=0.29) and higher than the acceptable PFS threshold (89.6%, p=0.043) for HN005. 44) Data from E3311, MC1273 and MC1675, deintensified adjuvant RT apparently results in 2-yr PFS in the order of 90%. 41,43,45) However, one should note different indications for concurrent adjuvant chemotherapy among trials.…”

Section: Roc Trial Boldly Attempted To Reduce Rt Dose To 30mentioning

confidence: 98%

“…evaluated the efficacy of 30 to 36 Gy adjuvant RT in TORS-resected, HPV-positive OPC with negative resection margin. [42][43][44][45] MC1273 is a single-arm phase 2 trial with 2 cohorts. 42) Patients with intermediate risks received 30 Gy twice-daily RT with weekly 15 mg/m 2 docetaxel.…”

Section: Roc Trial Boldly Attempted To Reduce Rt Dose To 30mentioning

confidence: 99%

Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer: Focused Review of Published Data

Kim¹

2022

Korean J Head Neck Oncol

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Human papillomavirus (HPV) is a causative agent for a subset of oropharyngeal cancer (OPC). The current standard of care (SOC) for locally advanced OPC is 70 Gy definitive radiotherapy (RT) concurrent with cisplatin, which entails significant proportions of acute and late grade 3 or higher toxicities. Accordingly, discovery of favorable prognosis of HPV-related OPC has led to enthusiasm to attenuate subspecialties therapy in multidisciplinary treatment. Diverse deintensification strategies were investigated in multiple phase 2 trials with an assumption that attenuated treatments result in comparable oncologic outcome and less toxicities compared with SOC. Several trials on chemotherapy deintensification revealed that concomitant administration of cisplatin is not to be omitted or substituted for cetuximab without compromising progression-free survival or local control. A transoral robotic surgery (TORS) is investigated as alternative local treatment, but TORS plus SOC or mild deintensified adjuvant RT showed similar toxicities and inferior oncologic outcomes compared with SOC definitive RT or moderately deintensified RT. However, it has been reported that TORS plus deintensified 30-36 Gy adjuvant RT results in excellent outcome and less late toxicity compared with SOC adjuvant RT. Several phase 2 trials reported apparently equivalent progression-free survival and local control and similar adverse effects with moderately deintensified 60 Gy RT compared with SOC 70 Gy RT. Further dose reduction below 60 Gy has been investigated using biology-directed approaches, which use response to induction chemotherapy or metabolic images to triage HPV-positive OPC for deintensified RT. In summary, these trials provide valuable insights for future directions. Available evidence consistently showed that moderately deintensified RT is effective and safe for HPV-positive OPC in both definitive and adjuvant settings. Concurrent cisplatin remains an essential component without which progression-free survival is significantly compromised for advanced HPV-positive OPC. A simple incorporation of TORS to SOC may be detrimental for oncologic outcome without anticipated toxicity reduction. Given the lack of level 1 evidence, it is prudent to curb an unjustified deviation from the current SOC and limit any deintensified strategies to clinical trials and adhere to the current SOC.

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“…11,12 A need to understand surgical disparities is especially poignant for oropharyngeal squamous cell carcinoma, a disease for which innumerable de-escalation protocols centered on transoral surgical techniques and novel adjuvant therapy protocols have been proposed and conducted over the last decade. [13][14][15][16][17] There is also evidence now of a rising diversity in the HPV(+)OPSCC cancer patient population, 18 an age range extending above 65, 19 and a wide range of smoking histories. 20 In addition, there has been a documented failure to appropriately test for HPV in minority communities, potentially underestimating the impact HPV has had on these communities.…”

Section: Introductionmentioning

confidence: 99%

Racial disparities in surgical treatment of oropharyngeal cancer: A Surveillance, Epidemiology, and End Results review

et al. 2023

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ObjectivesOropharyngeal squamous cell carcinoma (OPSCC) has been rising. This manuscript looks to explore racial disparities in the surgical management of OPSCC.MethodsA cancer database was queried for patients with OPSCC diagnosed from 2004 to 2017. Univariate and multivariable logistic regressions were used to evaluate associations between patient race/ethnicity, surgical treatment, and reasons for lack of surgery.Results37 306 (74.3%) patients did not undergo surgery, while 12 901 (25.7%) patients did. Non‐Hispanic black (NHB) patients were less likely to undergo surgery than other races (17.9% vs. 26.5%; p < 0.0001). In clinical discussions, the Asian, Native American, Hawaiian, Pacific Islander (ANAHPI), and unknown race group was more likely to directly refuse surgery when recommended (2.5% vs. 1.5%; p = 0.015).ConclusionRacial differences exist in treatment for OPSCC. NHB patients are less likely to actually undergo surgical management for OPSCC, while other patients are more likely to directly “refuse” surgery outright when offered.

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Non-Inferiority Margin and Nodal Analysis of De-Escalated Adjuvant Radiation Therapy (DART) for HPV-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Preplanned Pooled Analysis of MC1273 & MC1675

Cited by 5 publications

References 0 publications

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer

Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer: Focused Review of Published Data

Racial disparities in surgical treatment of oropharyngeal cancer: A Surveillance, Epidemiology, and End Results review

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