According to clinical results recently presented at the ESMO Asia 2015 Congress in Singapore, patients with EGFR-activating mutations in advanced lung cancer have more clinical benefits from being treated with afatinib as first-line therapy than with gefitinib.
In a worldwide, open-label, randomized Phase IIb LUX-Lung 7 (LL7) clinical trial, the permanent ErbB family blocker afatinib was found to significantly improve efficacy vs. gefitinib across a range of medically relevant trial outcomes, including progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR).
“Based on these results I would consider afatinib as the EGFR tyrosine kinase inhibitor (TKI) of choice for the first-line treatment for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC),” lead author, Professor Keunchil Park, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, said according to a recent news release.
Non-small-cell lung carcinoma (NSCLC) is an epithelial lung cancer; activating gene mutations in the epidermal growth factor receptor (EGFR) are more habitually seen in women and in non-smokers, occurring in 50% of Asians and in 10% of non-Asians.
Afatinib is a targeted therapy, classified as a Tyrosine Kinase inhibitor and an Epidermal Growth Factor Receptor (EGFR) inhibitor. Gefitinib also works by blocking the tyrosine kinase. Both drugs stop the cancer from growing and spreading. Both are also approved as treatment for naive patients, based on the outcomes of Phase III clinical trials, endorsing their superiority in comparison to chemotherapy. In contrast with gefitinib, a first-generation EGFR inhibitor, afatinib an irreversible ErbB family blocker is suggested to extend tumor response and delay the progression of the disease.
Results from the LUX-Lung 7 clinical trial indicate that afatinib might be a better treatment option for NSCLC naïve patients with positive EGFR-mutation who had not received prior treatment.
“First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib,” Park said. “Interestingly, the improvement in progression-free survival became more pronounced over time with a significantly higher proportion of patients alive and progression-free at 18 months (27% vs 15%; p=0.018) and 24 months (18% vs 8%; p=0.018), showing a greater long-term benefit of using the irreversible ErbB family blocker afatinib.”
Of the 319 patients that took part in the trial and who were randomly assigned to receive treatment either with afatinib or gefitinib, the results revealed that a significantly greater percentage responded to the first versus the second (70.0% vs. 56.0%). The median duration of response was of 10.1 months for afatinib and was of 8.4 months for gefitinib.
Concerning the tolerability profile, Park said: “Overall, the frequency of severe adverse events was similar in both arms with slightly different toxicity profiles. The adverse events observed with both treatments were predictable and manageable, leading to an equally low rate of treatment discontinuation in both arms (6.3%).”
ESMO spokesman Dr. Martin Reck from the Department of Thoracic Oncology, Hospital Grosshansdorf in Germany, who did not take part in the trial, mentioned that the individual patient and the presence of comorbidities will still guide the decision regarding the EGFR inhibitor.
“Following these trial results, afatinib will be one of the most attractive EGFR tyrosine kinase inhibitors. However, tolerability also plays a determining role in the selection and dosing of a tyrosine kinase inhibitor. The tolerability profiles between gefitinib and afatinib are different and the selection of the therapy will still be based on the individual clinical decision,” he said.
The initial analysis of overall survival numbers is intended to be available in 2016 and will provide more responses.
Commenting on future research directions for naive patients with non-small-cell lung cancer, Reck said: “One of the most important improvements that we have achieved in first-line treatment of NSCLC has been the implementation of molecular diagnosis. If a treatable molecular alteration like an EGFR mutation or an ALK translocation can be diagnosed, treatment with a targeted agent like an EGFR-TKI or an ALK-TKI would represent the most efficacious treatment. In all other patients platinum-based chemotherapy is still the standard. Current trials are evaluating whether immune checkpoint inhibitors will be superior to chemotherapy in patients with PDL-1 expressing tumours and whether monotherapy or combinations will replace chemotherapy in selected patients in the future.”
NSCLC is the most common type of lung cancer. Statistics for lung cancer include both small cell and non-small cell lung cancer. This year, an estimated 221,200 adults (115,610 men and 105,590 women) in the United States will be diagnosed with lung cancer. Lung cancer is the second most common cancer and the leading cause of cancer death for men and women. It is estimated that 158,040 (86,380 men and 71,660 women) deaths from this disease will occur this year.