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LUX-Lung 3: Afatinib extended PFS in EGFR-mutated lung adenocarcinomas
CHICAGO — Treatment with afatinib significantly extended PFS vs. standard chemotherapy treatment in patients with advanced lung adenocarcinomas that harbor epidermal growth factor receptor, according to results from the phase 3 LUX-Lung 3 trial.
Based on previously acquired data, EGFR-mutated lung adenocarcinoma often is linked to patients who have never smoked or patients of Asian descent. In the United States, an estimated 18,000 patients with lung adenocarcinomas with EGFR mutations are diagnosed each year.
Researchers conducted the study to investigate the safety and efficacy of afatinib (Tomtovok, Boehringer Ingelheim) — an oral therapy that blocks the broader ErbB family of receptors that are associated with the EGFR pathway, including HER-2 and HER-4, and can inactivate further cancer cell pathways — compared with the standard chemotherapy treatment of pemetrexed/cisplatin in patients with EGFR-mutation–positive advanced lung adenocarcinoma.
James Chih-Hsin Yang, MD, PhD, a professor at the National Taiwan University, and colleagues randomly assigned 345 patients to IV afatinib or standard combination chemotherapy treatment.
“LUX-Lung 3 is the largest and most robust phase 3 study in EGFR-mutated–positive patients and the first study to use pemetrexed/cisplatin as a comparator,” Yang said in a press conference. “This is a true global study that was performed in Asia, Europe, North America, South America and Australia.”
All participants had EGFR mutations that were identified through central testing, with imaging scans independently reviewed to assess treatment outcomes.
According to study results, treatment with afatinib led to a significantly prolonged PFS compared with standard chemotherapy (median 11.1 months vs. 6.9 months; HR=0.58; 95% CI, 0.43-0.78). In 308 patients with common mutations, such as deletion 19 or L858R, median PFS was 13.6 months in patients who received afatinib vs. 6.9 months in patients who received standard treatment (HR=0.47; 95% CI, 0.34-0.65). Researchers said the objective response rate also was significantly higher with afatinib (56% vs. 23%; P<.0001).
“We also showed that patients who received afatinib lived a longer period of time without further cancer progression, and they experienced better controlled disease and symptom control compared with patients receiving chemotherapy,” Yang said.
In addition, patients in the afatinib group demonstrated significant delay in time to deterioration of cancer-related symptoms of cough (HR=0.6; P=.0072) and dyspnea (HR=0.68; P=.0145).
The most common drug-related adverse events with afatinib were diarrhea (95%), rash (62%) and paronychia (57%), and the most common drug-related adverse events with chemotherapy were nausea (66%), decreased appetite (53%) and vomiting (42%). Drug-related adverse events led to discontinuation in 8% of patients in the afatinib group and 12% of patients in the chemotherapy group.
“The adverse effects that were detected with afatinib were consistent with EGFR features and were consistent with our prior phase 2 studies. [They] mainly consisted of diarrhea and skin rash, and [they] were manageable, predicable and reversible,” Yang said. “Additionally, patients who received afatinib actually reported better quality of life compared with chemotherapy.”
Disclosure: The researchers report serving as consultants or advisors to, as well as receiving honoraria from, Amgen, AstraZeneca, AVEO, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis, Daiichi Sankyo, Lilly, Merck Serono, Merrimack Pharmaceuticals and Taiho Pharmaceutical.
For more information:
Yang JC. Abstract #LBA7500. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Perspective
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This Phase III study is the largest ever trial in EGFR-mutated non–small cell lung cancer, and it is important because it shows that in this setting there is a clear clinical benefit for patients shown by the progression-free survival and quality-of-life improvement compared with first-line chemotherapy. The other exciting aspect of this study is that it represents a new generation of tyrosinase inhibitor, inhibiting the entire family of ErbB receptors, hoping to also see efficacy in patients who progress on current approved EGFR-inhibitor therapies.