Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy

Mehanna, Hisham M.; Kong, Anthony; Hartley, A.; Mistry, Pankaj; Dalby, Matthew J.; Fulton-Lieuw, Tessa; Robinson, Max; Gray, Alastair; Foran, B.; Şen, Mehmet; O’Toole, L.; Dyker, K.; Booz, H. Al; Molerón, R.; Brennan, Sean; Aynsley, E.; Chan, Anthony W.S.; Srinivasan, Devraj; Buter, Jan; Dunn, Janet A.

doi:10.1093/annonc/mdy424.046

Cited by 5 publications

(3 citation statements)

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“…4 Consequently, efforts to de-intensify therapy for HPV-associated OPSCC are actively being pursued to reduce treatmentrelated toxicities. [5][6][7][8][9][10] However, approximately 10%-25% of patients will develop disease recurrence depending on clinical risk factors and tumor biology.…”

Section: Introductionmentioning

confidence: 99%

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer

Chera

Kumar

Shen

et al. 2020

JCO

251

255

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PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHODS AND MATERIALS A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance. RESULTS One hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months). CONCLUSION Detection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.

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Section: Introductionmentioning

confidence: 99%

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer

Chera

Kumar

Shen

et al. 2020

JCO

251

255

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“…In the De-ESCALaTE HPV (ID: ISRCTN33522080), a randomized phase 3 trial, cetuximab treatment arm was associated with no reduction in treatment associated toxicity or morbidity, lower overall survival and high recurrence rate during the 2-year timeline, in comparison to the cisplatin arm. This suggested the continued utilization of cisplatin and radiotherapy for management [186]. A second trial -NRG Oncology RTOG 1016 (ID: NCT01302834), also reported similar results.…”

Section: Targeted Therapy Immunotherapy and Therapeutic Vaccinesmentioning

confidence: 75%

Exploring the role of HPV: from Sexually transmitted infection to Oropharyngeal Cancers

Srinivasan Rajsri,

Rao,

Vardhman

2024

Preprint

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Human papillomavirus (HPV) is one the most common sexually transmitted infections (STI), spreading through direct sexual contact to oropharynx and anogenital regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals’ HPV infection causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). Over 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. They present some unique infection driven cellular and molecular features, in comparison to other head and neck carcinomas (HNC), constituting distinct preventive, therapeutic and prognostic strategies - with significant strides made in this area. However, HPV+OPC are routinely detected at a later stage, adding to the disease burden and overall survival. In this review, we provide a summary of HPV from a STI to malignant transformation, while also parsing through the immune response environment. We further collate key literature around infection sites, diagnostics and clinical management, while throwing light on the current state of epidemiology, transmission, screening and prevention strategies. Indeed, our improving understanding of the disease’s molecular biology has added some success to the prognostic outcomes of certain HPV+OPC across clinical trials examining targeted therapeutics and immunotherapy. This work is directed towards improving our current understanding of HPV and associated oncogenic landscape, to guide screening, early detection, triaging and further prevention and management strategies.

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“…All these results are to be interpreted with caution. A recent trial showed there was a significant difference in the 2-year overall survival between cisplatin and cetuximab (97.5% vs. 89.4% respectively, p = 0.001, HR = 4.99, 95% CI: 1.70–14.67) and in 2-year recurrence rate (6.0% vs. 16.1% respectively, p = 0.0007, HR = 3.39, 95% CI: 1.61–7.19) in favor of cisplatin for HPV + OPC with exclusive CCRT [41].…”

Section: A Future Role In Treatment De-escalation For Hpv?mentioning

confidence: 99%

Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief

Karabajakian

Gau

Reverdy

et al. 2018

Cancers

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Induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) has been used for decades. However, its role is yet to be clearly defined outside of larynx preservation. Patients with high risk of distant failure might potentially benefit from sequential treatment. It is now widely accepted that TPF (docetaxel, cisplatin, and fluorouracil) is the standard IC regimen. Essays that have compared this approach with the standard of care, concurrent chemoradiotherapy (CCRT), are mostly inconclusive. Radiotherapy (RT) can be used in the post-IC setting and be sensitized by chemotherapy or cetuximab. Again, no consensus exists but there seems to be trend in favor of potentiation by cisplatin. Less toxic schemes of IC are tested as toxicity is a major issue with TPF. IC might have an interesting role in human papilloma virus (HPV)-related LA HNSCC and lead to CCRT de-escalation.

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Cetuximab versus cisplatin in patients with HPV-positive, low risk oropharyngeal cancer, receiving radical radiotherapy

Cited by 5 publications

References 0 publications

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer

Exploring the role of HPV: from Sexually transmitted infection to Oropharyngeal Cancers

Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief

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