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ESMO Asia 2015: Immunotherapy and Targeted Therapy Provide New Options for Difficult-to-Treat Head and Neck Cancer

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Key Points

  • Pembrolizumab in nasopharyngeal cancer showed an objective response rate of 22.2% and a median duration of response of 10.8 months.
  • The proportion of patients achieving clinical benefit with afatinib over methotrexate was four times greater in patients who did not receive prior EGFR-targeted therapy for recurrent or metastatic disease compared with patients who did receive prior therapy.
  • Afatinib showed more pronounced antitumor effects in patients with p16-negative disease and dysregulation of ErbB pathway–related biomarkers.

Novel strategies are being explored for difficult-to-treat and advanced head and neck cancer—the most heterogeneous group of malignancies that are generally associated with poor survival—and encouraging results have been presented in two trials at the first European Society for Medical Oncology (ESMO) Asia 2015 Congress in Singapore. 

In a phase I trial by Hsu et al (Abstract 315O), the immunotherapy agent pembrolizumab (Keytruda) showed promising antineoplastic activity in patients with heavily pretreated nasopharyngeal cancer, who currently have no effective treatment options. In a large phase II trial by Tahara et al (Abstract 314O), the targeted agent afatinib (Gilotrif) was effective in the second-line treatment of recurrent or metastatic squamous cell carcinoma (HNSCC) after failure with platinum-based therapy.

KEYNOTE-028

KEYNOTE-028 was a nonrandomized, multicohort, phase Ib trial that assessed the safety, tolerability, and preliminary efficacy of pembrolizumab in patients with programmed death ligand 1 (PD-L1)-positive advanced solid tumors, including 27 patients with nasopharyngeal cancer. “This study provides the first demonstration of clinical activity of a programmed cell death protein 1 (PD-1) inhibitor in 27 patients with recurrent/metastatic nasopharyngeal cancer, with an objective response rate of 22.2%,” said Chiun Hsu, MD, PhD, of the Department of Oncology, National Taiwan University Hospital. “We observed a median duration of response of 10.8 months. Pembrolizumab showed a manageable safety profile.”

Patients were heavily pretreated, including seven patients who had received at least five prior lines of systemic treatment. 

LUX-Head & Neck 1

Although squamous cell carcinoma of the head and neck is the most common type of cancer in this group, currently it also has a very poor prognosis with no well-defined standard of care after the failure of previous platinum-based therapy. The ErbB family of receptors (including EGFR, HER2, HER3, and HER4) plays an important role in tumorigenesis, and EGFR overexpression (occurring in ~90% of HNSCC cases) is associated with poor prognosis in HNSCC. 

The first results from the randomized, open-label, phase III LUX-Head & Neck 1 trial were presented earlier this year and showed that afatinib, an oral irreversible ErbB family blocker, significantly delayed tumor growth vs chemotherapy in patients following failure of their previous treatment, reducing the risk for disease progression by 20%.

Commenting on the efficacy outcomes in selected prespecified subgroups and biomarker-defined populations, Makoto Tahara, MD, PhD, of the Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan, said, “The progression-free survival benefit observed with afatinib over methotrexate was generally consistent across most prespecified patient subgroups analyzed, including subgroups based on geographic region (Asia, Europe, or North/Latin America). The ErbB family blocker showed benefit over methotrexate regardless of patient age (≥ 65 or < 65 years). More pronounced benefit was observed in patients who have not received prior EGFR-targeted therapy, and those with tumors harboring certain molecular biomarkers.”

The proportion of patients achieving clinical benefit with afatinib over methotrexate was four times greater in patients who did not receive prior EGFR-targeted therapy for recurrent or metastatic disease (37% reduction in risk of progression/death observed) compared with patients who did receive prior therapy (9% reduction in risk observed). Afatinib showed more pronounced antitumor effects in patients with p16-negative disease and dysregulation of ErbB pathway–related biomarkers (EGFR amplification, HER3-low, PTEN-high expression).

“These data provide important new insights into the efficacy outcomes in selected patient subgroups and may help identify those who may achieve the most benefit from the targeted therapy,” Dr. Tahara said. “Three additional phase III trials are ongoing, LUX-Head & Neck 3, LUX-Head & Neck 2 (global) and LUX-Head & Neck 4 (Asia), to further investigate the potential benefits of afatinib in patients with recurrent HNSCC progressing on/after platinum-based therapy and primary unresected locoregionally advanced HNSCC.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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