Bugatinib, a novel targeted agent for the treatment of advanced lung cancer, is a second-generation mesenchymal lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) that is currently used to treat patients with ALK-positive, metastatic non-small cell lung cancer (NSCLC), especially those with brain metastases.
First-generation ALK drugs, such as crizotinib, are often resistant 9 to 12 months after treatment, and brigatinib has shown significant efficacy in such resistant patients.
U.S. launch: a better option for ALK-positive advanced lung cancer
In April 2017, the U.S. Food and Drug Administration (FDA) approved the marketing of brigatinib for patients with ALK-positive metastatic NSCLC who are intolerant to crizotinib or whose disease has progressed after dosing.
The pivotal study that drove the launch of bucitinib was the ALTA study.
This study divided patients with ALK-positive NSCLC brain metastases into two groups: group A received 90 mg of oral brigatinib daily, and group B received 90 mg of oral brigatinib for the first 7 days, followed by 180 mg of oral brigatinib daily. The objective remission rate of brain metastases was found to be 46% and 67% in the two groups, respectively. The median intracranial progression-free survival was 15.6 months and 18.4 months, respectively. This suggests that buggitinib is effective in patients with brain metastases and is more effective when given orally at 180 mg daily.
U.S. guideline recommendation: advanced lung cancer, where buggitinib could ‘take over’ from crizotinib
In 2018, the National Comprehensive Cancer Network (NCCN) guidelines recommended that brigatinib be used as second-line therapy for patients with ALK-positive advanced NSCLC.
This recommendation is based on the results of another study that found that patients with ALK-positive NSCLC who were not treated with crizotinib had a progression-free survival time of 9.2 to 12.9 months after treatment with brigatinib.
Bugatinib is not yet available in China
Bugatinib is not yet approved for marketing in China, but a 2018 guideline recommends for ALK/ROS-1-positive patients with advanced NSCLC: After ALK-positive patients develop resistance to crizotinib, patients are encouraged to participate in clinical trials to gain access to new drug therapy, considering that second-generation drugs are not yet available in China. For patients who have access to second-generation drugs, it is recommended that after a second biopsy, the resistance point mutation status be analyzed and a sensitive second-generation drug be selected for treatment.
Studies underway
There are a number of studies exploring the scope, efficacy, and safety of pegatinib in the treatment of lung cancer, the two most important directions being whether pegatinib can replicate the existing findings in other countries/ethnic populations, and whether pegatinib can overcome resistance to similar drugs. For ease of navigation, two representative studies are briefly described below through tables.
| Table 1: Clinical studies of brugitinib for lung cancer | ||
| Clinical trial number | NCT03410108 | NCT03535740 |
| Study population | ALK-positive advanced NSCLC, Japanese patients | Progressive, ALK-positive advanced NSCLC after treatment with erlotinib or ceritinib (also second-generation ALK-targeting agents) |
| Trial status | Patient recruitment in progress | Not yet starting patient enrollment |
| Type of study | Phase 2 clinical study | Phase 2 clinical study |
| Main Results | No results yet | No results yet |
Summary
Bugatinib, a second-generation ALK-targeted agent, has high anticancer activity in patients who are resistant to crizotinib treatment, and those who have progressed, alleviating the dilemma that crizotinib is ineffective in ALK-positive NSCLC with cranial metastases.
Currently, the value of buggitinib has been recognized abroad and has taken its place in lung cancer treatment. We look forward to the launch of buggitinib in China as soon as possible.