Chemotherapy after first-line EGFR TKI fails to extend survival in advanced NSCLC
Click Here to Manage Email Alerts
Key takeaways:
- Platinum-doublet chemotherapy after initial response to EGFR TKI appeared associated with longer PFS but no OS benefit.
- The findings persisted regardless of whether patients received gefitinib or osimertinib.
CHICAGO — Platinum-doublet chemotherapy did not extend survival for patients with advanced nonsquamous non-small cell lung cancer who responded to EGFR tyrosine kinase inhibitor therapy, according to randomized phase 3 study results.
The regimen prolonged PFS but did not confer an OS benefit, findings presented at ASCO Annual Meeting showed.
“We are investigating the mechanisms of acquired resistance using tumor tissue and the liquid biopsy samples,” Shintaro Kanda, MD, of the department of hematology and clinical oncology at Shinshu University School of Medicine in Japan, said during a presentation.
Background and methods
EGFR TKI monotherapy is standard first-line treatment for patients with EGFR-mutated nonsquamous NSCLC. However, acquired resistance to EGFR TKI is a major challenge, contributing to poorer response and shorter survival, according to study background.
Results of a phase 2 study — which assessed the use of cisplatin and docetaxel with gefitinib (Iressa, AstraZeneca) — showed median PFS of 19.5 months and median OS of 48 months.
“Although several clinical studies suggested the benefits of concurrent combination of the first-generation EGFR TKI and platinum doublet chemotherapy, it is unclear whether such concurrent strategy is the most promising, and there are no data about osimertinib-based [combinations],” Kanda said.
Kanda and colleagues conducted the AGAIN study to evaluate whether platinum-doublet chemotherapy after initial response to EGFR TKI would prevent development of acquired resistance to EGFR TKI and extend survival.
The open-label, multicenter study included 501 adults (median age, 65 years; range, 20-74) with EGFR-mutated nonsquamous NSCLC.
All patients had advanced (86%) or recurrent disease (14%). All had exon 19 deletion (56%) or exon 21 L858R (44%), and all had ECOG performance status of 0 (47%) or 1 (53%).
Researchers assigned 250 patients to EGFR TKI alone — either 250 mg gefitinib daily or 80 mg osimertinib (Tagrisso, AstraZeneca) daily. Treatment in this group continued until disease progression.
The 251 patients assigned experimental therapy received gefitinib or osimertinib daily from days 1 to 56, followed by 2 weeks off. They then received three cycles of cisplatin and pemetrexed on days 71, 92 and 113, with resumption of gefitinib or osimertinib on day 134. Treatment continued until disease progression.
OS served as the primary endpoint. Secondary endpoints included PFS, response rate, adverse events, severe adverse events and proportion of EGFR T790M mutation-positivity in tumor samples at disease progression.
Results
Results showed longer PFS in the experimental group (18 months vs. 12 months; HR = 0.76; 95% CI, 0.62-0.92).
The PFS benefit persisted when researchers analyzed by treatment with gefitinib (14.4 months vs. 9.6 months; HR = 0.68; 95% CI, 0.54-0.86) vs. osimertinib (25.2 months vs. 20.4 months; HR = 0.81; 95% CI, 0.57-1.15).
However, researchers reported no difference in median OS between the standard and experimental groups (48 months vs. 48 months; HR = 0.98; 95% CI, 0.77-1.25).
This finding persisted when researchers analyzed outcomes by treatment with gefitinib (43.2 months vs. 45.6 months; HR = 1.01; 95% CI, 0.77-1.33) vs. osimertinib (not reached in either group; HR = 0.83; 95% CI, 0.48-1.44).
Collapse
Kanda S, et al. Abstract LBA9009. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
Click Here to Manage Email Alerts