Phase III data from the LUX-Lung 8 head-to-head trial, evaluating Gilotrif versus erlotinib in patients with advanced squamous cell carcinoma of the lung, demonstrated superior improvement in progression-free survival with Gilotrif.
The trial demonstrated that Gilotrif (afatinib) significantly reduced the risk of disease progression by 18 percent when compared to erlotinib and delayed tumor growth (PFS by independent review: 2.4 vs. 1.9 months; HR=0.82; p=0.043). Overall survival data are not yet mature.
Treatment with Gilotrif showed improvement in the secondary endpoint of disease control rate compared to erlotinib, 45.7 vs. 36.8 percent, respectively (p=0.020). Objective response rate was 4.8 percent in the Gilotrif arm compared to 3.0 percent in the erlotinib arm (p=0.233).
More patients reported an improvement in their global health status or quality of life (p=0.026) and cough (p=0.01) with Gilotrif versus erlotinib. No difference was observed with pain (p=1.0) and dyspnea (p=0.298) between groups. There was no significant difference in the time to deterioration across these four measures.
The trial results were presented at the ESMO 2014 Congress. Gilotrif, sponsored by Boehringer Ingelheim, is a once-daily kinase inhibitor that irreversibly binds and inhibits ErbB1, ErbB2 and ErbB4 receptors, and is not approved for SCC of the lung. Its safety and efficacy have not been established in this population.
LUX-Lung 8 is the largest prospective head-to-head trial to evaluate the superiority of Gilotrif versus erlotinib in patients with advanced squamous cell carcinoma of the lung. In the randomized, open-label trial, 795 patients with stage IIIB/IV SCC of the lung were randomized 1:1 to receive Gilotrif or erlotinib until disease progression. The planned primary analysis was based on 414 PFS events by independent review in the first 669 patients randomized (Gilotrif: 335, erlotinib: 334) while recruitment was ongoing.
A second head-to-head trial, LUX-Lung 7, is currently evaluating Gilotrif versus gefitinib as a first-line treatment in EGFR mutation positive non-small cell lung cancer patients.
Gilotrif is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations as detected by an FDA-approved test.
Phase II Study of Veliparib Improves PFS by 35 Percent
Interim results from an ongoing phase II study of veliparib in combination with chemotherapy showed a 35 percent improvement (P-value=0.14) in progression-free survival and a 30 percent improvement (P-value=0.21) in overall survival in patients with previously untreated metastatic or advanced non-small cell lung cancer.
The randomized, double-blind trial, which evaluated veliparib in combination with carboplatin and paclitaxel compared to placebo, was presented at the European Society for Medical Oncology 2014 Congress.
Patients in the squamous histology subgroup randomized to the veliparib arm demonstrated a PFS rate of 6.1 months compared to 4.1 months with carboplatin, paclitaxel and placebo (HR=0.50; P-value=0.06), and an OS rate of 10.3 months compared to 8.4 months (HR= 0.71; P-value=0.22).
Median PFS was improved from 4.2 to 5.8 months, and median OS was improved from 9.1 to 11.7 months. AbbVie, the drug’s sponsor, initiated a phase III clinical trial evaluating veliparib in patients with squamous NSCLC earlier in 2014 to confirm the results of this Phase 2 study.
AbbVie also presented data from a phase I study evaluating veliparib in combination with carboplatin and paclitaxel in Japanese patients with NSCLC that evaluated the preliminary efficacy of the treatment, as well as the recommended phase II dose.
The study demonstrated an overall response rate of 54.5 percent, with six patients achieving a partial response and four demonstrating stable disease ranging from 40 to 143 days. The study also demonstrated co-administration of carboplatin and paclitaxel had no significant effect on veliparib pharmacokinetics.
