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Dacomitinib improved PFS, toxicity in advanced NSCLC
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Dacomitinib exhibited significantly improved PFS with acceptable toxicity vs. erlotinib in patients with advanced non–small cell lung cancer.
“The results documented here for dacomitinib suggest that irreversible pan-HER inhibition may offer a new treatment option for patients with advanced NSCLC, potentially representing an effective alternative to reversible inhibition of [human epidermal growth factor receptor],” Suresh S. Ramalingam, MD, chief of thoracic oncology and director of medical oncology at the Emory University School of Medicine in Atlanta, and colleagues wrote.
Previous studies demonstrated that dacomitinib, compared with erlotinib (Tarceva, OSI Pharmaceuticals) and gefitinib (Iressa, AstraZeneca), exhibited higher potency HER kinase inhibition and greater anticancer activity in gefitinib- and erlotinib-sensitive and -resistant cell line and xenograft NSCLC models.
In addition, dacomitinib exhibited antitumor activity in phase 1 and 2 trials, indicating potential use in patients with progressive NSCLC after treatment with an EGFR tyrosine kinase inhibitor and one or more chemotherapy regimens.
Based on these data, Ramalingam and colleagues conducted a phase 2 randomized study comparing dacomitinib with erlotinib as second-/third-line treatment for patients with advanced NSCLC.
From November 2008 to October 2009, 188 patients were randomly assigned to dacomitinib (n=94) or erlotinib (n=94). The baseline characteristics of patients were balanced between treatment arms, except for baseline ECOG performance status 2 (dacomitinib, n=19; erlotinib, n=3), EGFR mutation (dacomitinib, n=19; erlotinib, n=11), and number of patients receiving two prior chemotherapy regimens (dacomitinib, n=40; erlotinib, n=29).
Exclusion criteria consisted of prior EGFR-targeted therapy, known leptomeningeal or symptomatic brain metastases, clinically significant gastrointestinal abnormalities, interstitial lung disease or uncontrolled cardiovascular disease.
According to study results, median PFS was 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR=0.66; 95% CI, 0.47-0.91).
In patients with KRAS wild-type tumors, median PFS was 3.71 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR=0.55; 95% CI, 0.35-0.85). Patients with KRAS wild-type/EGFR wild-type tumors demonstrated a median PFS of 2.21 months for those treated with dacomitinib and 1.84 months for those treated with erlotinib (HR=0.61; 95% CI, 0.37-0.99).
Median OS was 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR=0.8; 95% CI, 0.56-1.13).
“It is becoming widely accepted that, in addition to conventional efficacy outcomes such as PFS and OS, quality of life (from the patients’ perspective) is an important component of high-quality cancer care,” Ramalingam and colleagues wrote. “Although diarrhea, mucositis, and skin toxicity were more common with dacomitinib than with erlotinib, these [adverse events] were tolerable — as supported by discontinuation rates, dose reduction rates, and mean [patient-reported outcome] scores between arms — and improved over time.”
In addition, four treatment-related deaths were reported during the study resulting from pneumonia and pneumonitis in patients administered dacomitinib, and pneumonia and pulmonary embolism in patients administered erlotinib.
Disclosure: The researchers report employment, consulting or leadership positions with Boehringer Ingelheim, Genentech, Pfizer and Roche.
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