- Compared to the classic generation EGFR TKI gefitinib, daclatinib significantly prolongs patient survival and is more effective in patients of Asian descent.
- Dacitinib is still not available in China or the United States, but can be expected to be a first-line option in the clinic for NSCLC patients with EGFR mutations.
Women of Asian descent with nonsmoking NSCLC have a typical profile with a high probability of epidermal growth factor receptor (EGFR) gene mutations. Currently, EGFR tyrosine kinase inhibitors (TKI), a powerful tool for controlling this type of NSCLC, are the most commonly used class of targeted agents.
There are now three generations of EFGR TKI, and the second generation drugs bind irreversibly and pan-selectively to the target, giving them more significant efficacy by inhibiting multiple targets, including EGFR, while binding more tightly to the target.
Dacomitinib is a second-generation EGFR TKI that is primarily used for the treatment of advanced NSCLC with EGFR mutations. What is its efficacy and safety profile?
Recently, the top medical journal The Lancet Oncology published the results of a phase III clinical study (code name ARCHER 1050) by the team of Professor Yilong Wu at the Guangdong Lung Cancer Institute in China. It is the first phase III clinical study to directly compare the efficacy and safety of second-generation (daclatinib) and first-generation (gefitinib) EGFR TKI in patients with NSCLC with EGFR mutations.
Dacitinib: Dual benefit in progression-free survival and overall survival
In the study, patients in the daclatinib group had a median progression-free survival (PFS) of 14.7 months compared with 9.2 months in the gefitinib group, a full 5.5 months longer in the former.
On June 4, 2018, Professor Tony Mok of The Chinese University of Hong Kong orally reported the latest overall survival (OS) data from the study at the American Society of Clinical Oncology annual meeting. The study results showed that patients in the daclatinib group had an OS of 34.1 months and 26.8 months in the gefitinib group. The former was 7.3 months longer! This is significant for patients with advanced lung cancer and their families.
Dacitinib thus became the first second-generation drug to have a significant dual benefit in PFS and OS compared to a first-generation EGFR TKI.
Dacitinib: objective response rate similar to gefitinib, but with prolonged remission
Objective response rate (ORR) refers to the proportion of patients whose tumors shrink by a certain amount and remain in remission for a certain amount of time, and duration of remission (DOR) can be interpreted as the time it takes to reach the ORR criteria, and is one of the indicators to assess the efficacy of cancer drugs; a higher ORR and longer DOR indicate better efficacy. The results of the study showed (Table 1) that there was no significant difference in ORR between the two groups. However, the median DOR in the daclatinib group was longer than that in the gefitinib group.
Table 1, Comparison of ORR and median DOR in the daclatinib and gefitinib groups
| Dacitinib (n=227) | Gefitinib (n=225) | p-value | |
| Complete remission CR | 12 (5%) | 4 (2%) | |
| Partial mitigation of PR | 158 (70%) | 157 (70%) | |
| Stable SD | 30 (13%) | 27 (12%) | |
| Disease progression PD | 12 (5%) | 15 (7%) | |
| Unable to evaluate | 15 (7%) | 22 (10%) | |
| Objective Response Rate ORR | 170 (75%; 69 to 80) | 161 (72%; 65~77) | 0.4234 |
| Median duration of remission mDOR | 14.8 (12.0 to 17.4) | 8.3 (7.4 to 9.2) | <0.0001 |
Dacitinib: safety and tolerability consistent with gefitinib
Dacitinib and gefitinib showed a more consistent safety profile, with the most common adverse events being acne, diarrhea, and abnormal liver function.
Dacitinib: significant benefit in Asian patients
It is worth noting that 231 of the 452 patients enrolled were Chinese patients. The results of the study suggest that Asian populations are more likely to benefit from daclatinib.