Phase 2 MAESTRO Study Fails to Meet Primary Endpoint of PFS in Head and Neck Cancer


The study of temsirolimus and cetuximab versus temsirolimus alone in patients with recurrent or metastatic cetuximab-resistant head and neck cancer did not meet its primary end point of improved progression-free survival.

Results from the phase 2 MAESTRO study of temsirolimus (Torisel) and cetuximab (Erbitux) versus temsirolimus alone in patients with recurrent or metastatic cetuximab-resistant head and neck cancer indicated that the study did not meet its primary end point of improvement in progression-free survival (PFS).

However, the results, published in Cancer, suggested that the combination of temsirolimus and cetuximab did induce responses in this patient population with good tolerability. Therefore, the post hoc observation of activity in patients with acquired resistance after prior benefit from cetuximab monotherapy may warrant further investigation. 

“Overall, this was a negative study, but further mechanistic and clinical investigation of the combination as a salvage treatment option, particularly for patients with prior benefit from cetuximab monotherapy, may be warranted,” the authors wrote.

In this multicenter, randomized, phase 2 study, patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with documented progression on cetuximab in any line in the recurrent or metastatic setting received 25 mg of temsirolimus weekly plus 400/250 mg/m2 of cetuximab weekly or single-agent temsirolimus. The primary outcome was PFS in the combination arm versus the single-agent arm. Secondary outcomes included response rates, overall survival (OS), and toxicity.

In total, 80 patients were included in the trial. Ultimately, PFS was not significantly different between the 2 arms (log-rank P = 0.73). The median PFS time was 105 days for the temsirolimus plus cetuximab combination arm (95% CI, 70-136 days) and 105 days for the single-agent temsirolimus arm (95% CI, 77-147 days). Similarly, OS was not significantly improved. The median OS time was 177 days for the combination arm (95% CI, 146-247 days) and 176 days for the single-agent arm (95% CI, 131-316 days).

Notably though, the response rate was 12.5% in the combination arm (5 responses, including 1 complete response [CR; 2.5%]) and 2.5% in the single-agent arm (1 partial response [PR]; P = 0.10). Responses were deemed clinically meaningful in the combination arm (range, 3.6-9.1 months), but not in the single-agent arm (1.9 months).

“Because the [temsirolimus]-alone comparator arm did not show meaningful activity, neither the response rate nor the duration of response was likely driven by [temsirolimus] alone,” the authors wrote. “Furthermore, some patients who progressed on [temsirolimus] and crossed over to the combination showed some disease stabilization, and this indicated that the efficacy was due to the combination.”

The most common grade 3 or higher adverse events (AEs) observed in >20% of patients in both arms were fatigue, electrolyte abnormalities, and leukopenia. No grade 5 hematologic adverse events were observed in either arm. However, 2 grade 5 nonhematologic adverse events were reported in the combination arm; 1 with a pulmonary hemorrhage and another with death not otherwise specified.

“Overall, this is a negative study, and the median PFS and OS do not support development in the overall population of patients with EGFR-refractory HNSCC,” the authors concluded. “The identification of a predictive biomarker to enrich a population with a higher rate of benefit might support further development to provide a clinically meaningful treatment option for patients for whom prior cetuximab therapy has failed.”

Though biomarker development for cetuximab therapy in this space has not yet been successful, researchers suggested that recent biomarker analyses with newer agents suggest that HPV status and PTEN/PI3K influence upfront anti-EGFR therapy efficacy for HNSCC, warranting further exploration.


Seiwert TY, Kochanny S, Wood K, et al. A Randomized Phase 2 Study of Temsirolimus and Cetuximab Versus Temsirolimus Alone in Recurrent/Metastatic, Cetuximab-Resistant Head and Neck Cancer: The MAESTRO Study. Cancer. doi: 10.1002/cncr.32929.

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