Head and neck cancer: more treatment options available21 Dec 2015
Novel strategies are on the way for difficult-to-treat and advanced head and neck cancer, the most heterogeneous group of malignancies which are generally associated with poor survival.
Manageable safety profile and positive clinical activity for pembrolizumab
In a Phase 1 trial1, the immunotherapy agent pembrolizumab has shown promising antineoplastic activity in patients with heavily pretreated nasopharyngeal cancer, who currently have no effective treatment options. In a large Phase 2 trial, the targeted agent afatinib was effective in the second-line treatment of recurrent or metastatic squamous cell carcinoma (HNSCC) after failure with platinum-based therapy.
KEYNOTE-028 is a non-randomized, multicohort, Phase 1b trial which assessed the safety, tolerability and preliminary efficacy of pembrolizumab in patients with PD-L1 positive advanced solid tumors, including 27 patients with nasopharyngeal cancer. "This study provides the first demonstration of clinical activity of a PD-1 inhibitor in 27 patients with recurrent/metastatic NPC, with an objective response rate of 22.2%," says study author Professor Chiun Hsu, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
"We observed a median duration of response of 10.8 months. Pembrolizumab showed a manageable safety profile". Patients were heavily pretreated, including 7 patients who had received at least 5 prior lines of systemic treatment.
Very poor prognosis for squamous cell carcinoma of the head and neck
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 3 LUX-Head & Neck 1 trial2 showed that afatinib, an oral irreversible ErbB family blocker, significantly delayed tumor growth versus chemotherapy in patients following failure of their previous treatment, reducing the risk for disease progression by 20%.
Commenting on the efficacy outcomes in selected pre-specified subgroups and biomarker-defined populations, first author Dr. Makoto Tahara, 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 pre-specified patient subgroups analyzed, including subgroups based on geographical 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.
“Afatinib showed more pronounced antitumor effects”
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 to identify those who may achieve the most benefit from the targeted therapy," Tahara said. "Three additional Phase 3 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."Source: Medical News Today