Epidermal Growth Factor Receptor Blockade in Head and Neck Cancer: What Remains?

Jelinek, Michael J.; Vokes, Everett E.

doi:10.1200/jco.19.01981

Cited by 7 publications

(13 citation statements)

References 38 publications

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“…Interestingly, in a post‐hoc exploratory subgroup analysis, we demonstrated a 0% ORR in HPV‐positive patients on both arms, compared with 12.5% (TC arm) and 13% (C arm) in HPV‐negative patients, driven by cetuximab therapy . These results are consistent with other reports that EGFR inhibitors, including cetuximab, appear to be less active in patients with HPV‐positive/p16‐positive HNSCC . Comprehensive genomic analysis has revealed that EGFR gene amplification is common in HPV‐negative HNSCC but almost nonexistent in HPV‐positive HNSCC .…”

Section: Discussionsupporting

confidence: 90%

“…18 These results are consistent with other reports that EGFR inhibitors, including cetuximab, appear to be less active in patients with HPV-positive/ p16-positive HNSCC. 6,19,20 Comprehensive genomic analysis has revealed that EGFR gene amplification is common in HPV-negative HNSCC but almost nonexistent in HPV-positive HNSCC. 9,18,21 This evidence suggests that patients with HPV-positive HNSCC may not be a suitable population for anti-EGFR therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) is expressed at high levels in the majority of head and neck cancers, and its expression is associated with a poor prognosis . Treatment with the anti‐EGFR antibody cetuximab (either alone or in combination with chemotherapy) is approved in the United States for patients with recurrent/metastatic disease . Despite frequent EGFR expression in HNSCC, the objective response rate to cetuximab monotherapy is only 10% to 13% versus 36% in combination with chemotherapy .…”

Section: Introductionmentioning

confidence: 99%

“…4 Treatment with the anti-EGFR antibody cetuximab (either alone or in combination with chemotherapy) is approved in the United States for patients with recurrent/metastatic disease. 1,5,6 Despite frequent EGFR expression in HNSCC, the objective response rate to cetuximab monotherapy is only 10% to 13% 5 versus 36% in combination with chemotherapy. 1 Given this modest clinical activity, investigation of combination approaches that target escape signaling pathways has been of interest 7,8 to improve efficacy.…”

Section: Introductionmentioning

confidence: 99%

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A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Kochanny

Worden

Adkins

et al. 2020

Cancer

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BACKGROUND: MET signaling is a well described mechanism of resistance to anti-EGFR therapy, and MET overexpression is common in head and neck squamous cell carcinomas (HNSCCs). In the current trial, the authors compared the oral MET inhibitor tivantinib (ARQ197) in combination with cetuximab (the TC arm) versus a control arm that received cetuximab monotherapy (C) in patients with recurrent/ metastatic HNSCC. METHODS: In total, 78 evaluable patients with cetuximab-naive, platinum-refractory HNSCC were enrolled, including 40 on the TC arm and 38 on the C arm (stratified by human papillomavirus [HPV] status). Patients received oral tivantinib 360 mg twice daily and intravenous cetuximab 500 mg/m 2 once every 2 weeks. The primary outcome was the response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), and secondary outcomes included progression-free and overall survival. After patients progressed on the C arm, tivantinib monotherapy was optional. RESULTS: The response rate was 7.5% in the TC arm (N = 3; 1 complete response) and 7.9% in the C arm (N = 3; not significantly different [NS]). The median progression-free survival in both arms was 4 months (NS), and the median overall survival was 8 months (NS). Both treatments were well tolerated, with a trend toward increased hematologic toxicities in the TC arm (12.5% had grade 3 leukopenia). The response rate in 31 HPV-positive/p16-positive patients was 0% in both arms, whereas the response rate in HPV-negative patients was 12.7% (12.5% in the TC arm and 13% in the C arm). Fifteen patients received tivantinib monotherapy, and no responses were observed. CONCLUSIONS: Combined tivantinib plus cetuximab does not significantly improve the response rate or survival compared with cetuximab alone but does increase toxicity in an unselected HNSCC population. Cetuximab responses appear to be limited to patients who have HPV-negative HNSCC. MET-aberration-focused trials for HNSCC and the use of higher potency, selective MET inhibitors remain of interest. Cancer 2020;126:2146-2152.We thank the patients and their families for their participation and the clinical and research staff at the participating institutions for their hard work. We also thank Shanda Lentz for her contributions while preparing the article. We thank the following faculty for their contributions to this trial and for entering their patients: : Data acquisition, statistical analysis, article preparation, and writing. Francis P. Worden: Patient enrollment. Douglas R. Adkins: Patient enrollment. Dean W. Lim: Patient enrollment. Julie E. Bauman: Patient enrollment. Stephanie A. Wagner: Patient enrollment. Ryan J. Brisson: Data acquisition and editing. Theodore G. Karrison: Formal statistical analysis. Walter M. Stadler: Trial management and advisor. Everett E. Vokes: Patient enrollment and methodology. Tanguy Y. Seiwert: Conceptualization, methodology, patient enrollment, article preparation, and writing.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Kochanny

Worden

Adkins

et al. 2020

Cancer

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“…However, these results were ultimately biased by the everlasting absence of a direct comparison with concurrent cisplatin. In addition, the lack of predictive biomarkers for anti-EGFR blockade in head and neck squamous cell carcinoma (HNSCC) [13] and the suboptimal tolerability of cetuximab in clinical practice [14,15] limited its use to a large extent. Controversial data emerged on its specific efficacy for HPV positive patients, as well [16].…”

Section: Discussionmentioning

confidence: 99%

De-intensification for HPV positive oropharyngeal cancer: and yet it moves!

Bonomo¹,

Livi

2020

Clinical and Translational Radiation Oncology

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Epidermal growth factor receptor‑targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real‐world study

Zhang,

Lang

et al. 2024

MedComm

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Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.

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Epidermal Growth Factor Receptor Blockade in Head and Neck Cancer: What Remains?

Cited by 7 publications

References 38 publications

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

De-intensification for HPV positive oropharyngeal cancer: and yet it moves!

Epidermal growth factor receptor‑targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real‐world study

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