Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design

Fleming, C. Richard; Ward, Matthew C.; Woody, N.M.; Joshi, Nikhil; Greskovich, J.F.; Rybicki, Lisa; Xiong, David D.; Contrera, Kevin J.; Chute, Deborah J.; Milas, Zvonimir L.; Frenkel, Catherine; Brickman, Daniel; Carrizosa, Daniel R.; Ku, Jamie; Prendes, Brandon; Lamarre, Eric; Lorenz, Robert R.; Scharpf, Joseph; Burkey, Brian B.; Schwartzman, L.; Geiger, J.L.; Adelstein, David J.; Koyfman, Shlomo A.

doi:10.1016/j.oraloncology.2020.105046

Cited by 11 publications

(8 citation statements)

References 20 publications

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“…The same was true in recurrent/metastatic (R/M) HNSCC. [ 11 , 12 , 13 ] To account for disparate outcomes between HPV+ and HPV− disease, genomic signatures have been previously explored [ 14 ]. For instance, PIK3CA mutations are common in HPV+ cancers, while TP53 mutations are rare [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

Shaikh

McGrath

Hughes

et al. 2021

Cancers

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Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better prognosis compared to HPV−negative disease. Immune checkpoint blockade (ICB) is the standard of care for R/M HNSCC. However, whether HPV and its surrogate marker, p16, portend an improved response to ICB remains controversial. We queried the Caris Life Sciences CODEai database for p16+ and p16− HNSCC patients using p16 as a surrogate for HPV. A total of 2905 HNSCC (OPSCC, n = 948) cases were identified. Of those tested for both HPV directly and p16, 32% (251/791) were p16+ and 28% (91/326) were HPV+. The most common mutation in the OPSCC cohort was TP53 (33%), followed by PIK3CA (17%) and KMT2D (10.6%). TP53 mutations were more common in p16− (49%) versus the p16+ group (10%, p < 0.0005). Real-world overall survival (rwOS) was longer in p16+ compared to p16− OPSCC patients, 33.3 vs. 19.1 months (HR = 0.597, p = 0.001), as well as non-oropharyngeal (non-OP) HNSCC patients (34 vs. 17 months, HR 0.551, p = 0.0001). There was no difference in the time on treatment (TOT) (4.2 vs. 2.8 months, HR 0.796, p = 0.221) in ICB-treated p16+ vs. p16− OPSCC groups. However, p16+ non-OP HNSCC patients treated with ICB had higher TOT compared to the p16− group (4.3 vs. 3.3 months, HR 0.632, p = 0.016), suggesting that p16 may be used as a prognostic biomarker in non-OP HNSCC, and further investigation through prospective clinical trials is warranted.

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Section: Introductionmentioning

confidence: 99%

Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

Shaikh

McGrath

Hughes

et al. 2021

Cancers

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“…In a proposed treatment algorithm for patients with metastatic HNSCC, Tang et al 26 suggested that patients with three or fewer metastases benefit best from curative intent treatment, whereas patients with more than three metastases should receive systemic treatment. Fleming et al 27 reported decreased OS with increasing number of metastases, with a median OS of 41.2 versus 17.2 versus 10.8 months for 1 versus 2-4 versus 5 or more lesions, respectively (p 5 .007). 27 Patients with HPV-related oropharynx oligometastatic HNSCC have better OS and disease-free survival than HPVÀ counterparts (2-year OS, 60% vs. 25%, p < .05).…”

Section: Second-line Therapymentioning

confidence: 97%

“…Fleming et al 27 reported decreased OS with increasing number of metastases, with a median OS of 41.2 versus 17.2 versus 10.8 months for 1 versus 2-4 versus 5 or more lesions, respectively (p 5 .007). 27 Patients with HPV-related oropharynx oligometastatic HNSCC have better OS and disease-free survival than HPVÀ counterparts (2-year OS, 60% vs. 25%, p < .05). 28,29 Lee et al 30 showed that patients with metachronous oligometastatic HPV1 oropharynx carcinoma will benefit from initial definitive metastasis-directed therapy compared with upfront systemic therapy (median OS not reached vs. 40.7 months, p 5 .021).…”

Section: Second-line Therapymentioning

confidence: 97%

Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges

Wise‐Draper

Bahig

Karivedu

et al. 2022

American Society of Clinical Oncology Educational Book

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Management of metastatic head and neck squamous cell carcinoma is evolving as new systemic therapies have led to improvements in survival, and as advances in locoregional therapy and the increased numbers of patients with HPV-associated cancers who develop oligometastases raise the possibility of ablation of limited numbers of metastases. We review the data regarding first-line immunotherapy in PD-L1–expressing metastatic head and neck squamous cell carcinoma, the experience with aggressive local management of oligometastases, and promising novel immunotherapies, targeted therapies, and HPV-specific treatments. For patients with metastatic head and neck squamous cell carcinoma that is PD-L1 expressing, first-line systemic therapy is pembrolizumab or pembrolizumab with chemotherapy. Inclusion of chemotherapy is associated with higher objective response proportion in all biomarker subgroups and may have a greater impact on survival in HPV-associated cancers. For patients with oligometastatic disease, particularly when metastases are metachronous, current evidence supporting the role of local ablation is limited to a small number of retrospective studies. Based on retrospective data, patients with a smaller number of metastases, lung metastases, and/or virally associated head and neck squamous cell carcinoma are most likely to benefit from an aggressive ablative approach. Additionally, we review emerging evidence for targeted therapy in metastatic head and neck squamous cell carcinoma, including with agents that inhibit mutant HRAS or NOTCH1, or overexpressed EGFR. Studies of antiangiogenic agents in combination with immune checkpoint blockade, and combination immunotherapy, are also under study.

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“…In the context of surgical resection of HNSCC pulmonary metastases, the presence of multiple pulmonary nodules significantly decreases the survival probability for oligometastatic disease [ 40 , 41 ]. Fleming et al reported decreased efficacy of radical metastasis-directed treatment associated with systemic therapy with an increasing number of metastases in metastatic HPV-positive HNSCC; for 1, 2–4 and ≥5 metastasis, median OS was 41.2, 17.2 and 10.8 months, respectively ( p = 0.007) [ 42 ]. In a proposed treatment algorithm for patients with metastatic HNSCC, Tang et al proposed that patients with ≤3 metastatic lesions benefit best from curative intent treatment, whereas patients with >3 metastatic lesions may benefit best from upfront systemic treatment [ 43 ].…”

Section: Selecting Optimal Hnscc Patients For Aggressive Ablationmentioning

confidence: 99%

Oligometastatic Head and Neck Cancer: Challenges and Perspectives

Bahig

Huang

O’Sullivan

2022

Cancers

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A minority of patients with metastatic head and neck squamous cell carcinoma (HNSCC) present with oligometastatic disease. Oligometastasis not only reflects a disease state, but might also present an opportunity for cure in the metastatic setting. Radical ablation of all oligometastatic sites may confer prolonged survival and possibly achieve cure in some patients. However, substantial debate remains about whether patients with oligometastatic disease could benefit from curative intent therapy or whether aggressive treatments expose some patients to futile toxicity. Optimal selection of patients, carefully balancing the currently known prognostic factors against the risks of toxicity is critical. Emerging evidence suggests that patients with a limited burden of disease, viral-related pharyngeal cancer, metachronous metastasis and lung-only metastasis may benefit most from this approach. Efforts are underway to identify biomarkers that can detect oligometastasis and better select patients who would derive the maximum benefit from an aggressive radical approach. The combination of radiotherapy and immunotherapy promises to enhance the anti-tumoral immune response and help overcome resistance. However, optimization of management algorithms, including patient selection, radiation dose and sequencing, will be critical in upcoming clinical trials. This review summarizes recent knowledge about the characteristics and investigational efforts regarding oligometastasis in HNSCC.

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Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design

Cited by 11 publications

References 20 publications

Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes

Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges

Oligometastatic Head and Neck Cancer: Challenges and Perspectives

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