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Gefitinib plus docetaxel failed to improve OS in SCCHN
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The addition of gefitinib to docetaxel in poor-prognosis patients with squamous cell carcinoma of the head and neck was well tolerated but did not improve clinical outcomes, according to results of a phase 3 trial.
Median OS among patients assigned to gefitinib (Iressa, AstraZeneca) plus docetaxel was 7.3 months, compared with 6 months for patients treated with docetaxel alone. The difference did not reach statistical significance.
The trial was halted early during interim analysis.
“This was one of the first phase 3, randomized trials in patients with previously treated or compromised performance status,”Athanassios “Ethan” Argiris, MD, FACP, professor and chief in the division of hematology and oncology at the University of Texas Health Science Center at San Antonio, told HemOnc Today.
Argiris and colleagues hypothesized that the therapeutic efficacy of docetaxel would be enhanced with the addition of gefitinib in patients with SCCHN. The placebo-controlled ECOG trial included 270 patients with either recurrent or metastatic SCCHN. The cohort included patients with an ECOG performance status of 2, or patients with a performance status of 0 to 2 who had undergone prior treatment with chemotherapy.
Patients were randomly assigned to arm A (weekly docetaxel plus placebo) or arm B (weekly docetaxel plus oral daily gefitinib 250 mg) until disease progression, at which time, patients assigned to arm A could receive single-agent gefitinib.
Researchers observed no significant difference in time to progression between study arms (2.1 months for placebo vs. 3.5 months for gefitinib). Adverse events included higher rates of grade 3 or 4 diarrhea in the gefitinib arm; however, other adverse events were similar between the two arms.
In an unplanned subset analysis, researchers observed improvements in OS among patients aged younger than 65 years assigned to gefitinib (7.6 months vs. 5.2 months; P=.04). Regardless of the treatment arm, a trend for improved OS was observed among those with c-MET wild-type (5.7 months vs. 3.6 months; P=.09).
Of the 18 patients assigned to arm A who received gefitinib after disease progression, one patient had a partial response.
“Chemotherapy alone was not effective in this setting and new therapeutic strategies are highly warranted,” Argiris said. “We were hoping for a survival benefit with the addition of gefitinib to docetaxel, but this was not demonstrated in unselected patients with recurrent or metastatic head and neck cancers. Nevertheless, a survival benefit was seen in the subset of patients younger than 65 years, who could tolerate the combination better. Age may affect the ability of patients to tolerate newer therapies and is a factor to be considered in the design of future clinical trials in head and neck cancers.”
Athanassios “Ethan” Argiris, MD, FACP, can be reached at UT Health Science Center at San Antonio, Attn: Dr. Athanassios Argiris, 7979 Wurzbach Road MC8232, Zeller Building — 4th Floor, Room Z418, San Antonio, TX 78229; email: argiris@uthscsa.edu.
Disclosure: Argiris reports honoraria and research funding from AstraZeneca.
Perspective
Back to TopBarbara Burtness, MD
This trial was designed before cetuximab (Erbitux; Bristol-Myers Squibb, Eli Lilly) was approved for the treatment of head and neck cancers, but cetuximab became commercially available during the time that the study was accruing. A proportion of patients — particularly on the control arm — may have received cetuximab upon progression, thus confounding the primary endpoint of OS.
The study was closed early because of an interim futility analysis centered on OS, and not adjusted for post-study use of cetuximab. This compromised the power of some of the secondary analyses, in particular for PFS and response. Nonetheless, the study is informative. Firstly, it confirms the utility of docetaxel as a second-line treatment in patients with recurrent/metastatic head and neck cancers, including in the elderly. Second, in light of the early study closure and the possibility of confounding by post-study use of cetuximab, the study may still be consistent with modest clinical benefit from the addition of gefitinib. The difference in survival between patients with c-MET mutation and c-MET wild type approached significance, and it suggests that Met inhibition will be a useful target in these patients.
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