Afatinib Extends Advanced Squamous NSCLC Overall Survival

Advanced squamous non-small-cell lung cancer survival is boosted by the tyrosine kinase inhibitor afatinib compared with erlotinib therapy

medwireNews: Second-line afatinib offers a significant overall survival (OS) benefit over erlotinib for patients with stage III/IV squamous non-small-cell lung cancer (NSCLC), LUX-Lung 8 trial results indicate.

OS analysis from the phase III trial was reported this week at the annual meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, Illinois, USA, and follows earlier reports of a progression-free survival (PFS) advantage for the irreversible tyrosine kinase inhibitor (TKI) targeting the Epidermal growth factor receptor (EGFR) and ErbB-2.

The 398 patients randomly assigned to receive afatinib 40 mg/day had a 19% lower risk of death than the 397 patients given the reversible anti-EGFR TKI erlotinib 150 mg/day, with median OS of 7.9 versus 6.8 months, reported the LUX-Lung 8 investigators.

And this OS advantage was found after 6 months (63.6 vs 54.6%), 12 months (36.4 vs 28.2%) and 18 months (22.0 vs 14.4%) of follow-up, said Jean-Charles Soria, from Gustave Roussy Cancer Campus and University Paris-Sud in France, and team.

Afatinib also offered significantly better outcomes than erlotinib in terms of median PFS (2.6 vs 1.9 months), objective response rate (5.5 vs 2.8%) and the disease control rate (50.5 vs 39.5%).

In addition, patients given afatinib were significantly more likely to have gains in global health status and quality of life (QoL) than erlotinib-treated counterparts (35.7 vs 28.3%), as well as improvements in cough (43.4 vs 35.2%) and dyspnoea (51.3 vs 44.1%).

Afatinib and erlotinib had “comparable” adverse event profiles with grade 3 or more severe side effects reported for 57.1% and 57.5% of patients, respectively. Afatinib-treated patients were more likely to experience grade 3 or 4 diarrhoea and Stomatitis than the erlotinib group, while rash or acne was more common with erlotinib.

“With a manageable [adverse event] profile, added QoL benefit, and symptom control seen in [LUX-Lung 8], [afatinib] should be preferred over [erlotinib] for these [patients]”, the researchers conclude.

However, discussing the study results, Gregory Riely, from Memorial Sloan Kettering Cancer Center in New York, USA, questioned whether an EGFR TKI is the “drug of choice” for patients with squamous NSCLC.

Between enrollment for the LUX-Lung 8 trial in 2012 and the primary OS analysis in 2015, the Vascular endothelial growth factor receptor 2 inhibitor ramucirumab and the anti-PD-1 inhibitor nivolumab were approved in the USA for this patient population, he noted.

Nivolumab and ramucirumab plus docetaxel both have higher response rates in squamous cell lung cancer than afatinib and erlotinib, at 20% and 27% versus 6% and 3%, respectively. Nivolumab and ramucircumab plus docetaxel also have better reported median OS, at 9.2 and 9.5 months versus 7.9 and 6.8 months, respectively.

“Afatinib is the EGFR TKI of choice in squamous cell lung cancer but I wouldn’t choose an EGFR TKI”, Gregory Riely therefore concluded, adding: “Understanding why the rare patient responds is helpful and we look forward to the report of the [next generation sequencing] analysis.”

Reference

Soria J-C, Felip E, Cobo M, et al. Afatinib (A) vs erlotinib (E) as second-line therapy of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following platinum-based chemotherapy: Overall survival (OS) analysis from the global phase III trial LUX-Lung 8 (LL8).J Clin Oncol 33, 2015 (suppl; abstr 8002)

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