Chemotherapy Better Than EGFR TKIs for First- and Second-Line Treatment of EGFR Exon 20+ NSCLC

Chemotherapy demonstrated superior progression-free survival (PFS) to multiple EGFR tyrosine kinase inhibitors (TKIs) as first- or second-line treatment of patients withEGFR-mutant exon 20 non—small cell lung cancer (NSCLC). This finding is based on results from the largest real-world study of patients withEGFRexon 20 mutations conducted in China. 

Data were pulled from medical records from different institutions in China and retrospectively analyzed for the treatment patterns and outcomes of Chinese patients to determine differences in patients treated with chemotherapy versus EGFR TKIs.

A total of 165 patient records were reviewed from 99 different institutions. Thirty-nine molecular variants were identified in the patients and the majority of these patients (23%) had V769_D770insASV. The second most common insertion was D770_NT71insSVD, which was found in 17.6% of patients. Some patients had co-existing genetic alterations including p53 mutations (65%),EGFRamplifications (13.5%), PTENmutations (10.8%), PIK3CAmutations (7.7.%), MYCamplifications (6.2%), RB1mutations (6.2%),BIMdeletion polymorphisms (6.2%), and one patient had exon 19 deletion and T790M (0.6%). Twenty-three percent had central nervous system (CNS) metastasis at baseline.

In terms of treatment type, chemotherapy regimens in the evaluated records mainly included pemetrexed, docetaxel, paclitaxel, gemcitabine, and albumin-bound paclitaxel (Abraxane) combined with platinum chemotherapy with or without bevacizumab (Avastin). The first-generation EGFR TKIs used were predominantly gefitinib (Iressa), erlotinib (Tarceva), and icotinib ([Conmana], approved and sold only in China). The only second-generation EGFR TKI used was afatinib (Gilotrif). Some patients were also treated with the third-generation EGFR TKI, osimertinib (Tagrisso). Immune checkpoint inhibitors, most commonly pembrolizumab (Keytruda) and nivolumab (Opdivo), were used for some patients.

Data on first-line treatment were available for 100 out of 127 patients withEGFRexon 20—positive NSCLC without CNS metastasis. Overall, 84 patients received chemotherapy first-line and 16 received EGFR TKIs. The median PFS among patients treated with chemotherapy was 6.5 months (95% CI, 4.9-8.1) compared with 2.9 months (95% CI, 2.1-3.7) among patients treated with EGFR TKIs (HR, 0.323; 95% CI, 0.174-0.598;P<.001).

A significantly prolonged PFS was also observed with chemotherapy treatment in patients with CNS metastasis. Chemotherapy led to a median PFS of 3.6 months (95% CI, 0-8.0), and treatment with EGFR TKIs led to a median PFS of 2.0 months (95% CI, 0.8-3.2).

When treated in the second line (n = 52), the median PFS was 4.0 months (95% CI, 3.2-4.8) with chemotherapy and 2.0 months (95% CI, 1.1-2.9) with EGFR TKIs (HR, 0.700; 95% CI, 0.357-1.374;P= .342).

In the select patients who received bevacizumab with chemotherapy (n = 39), the median PFS was longer at 7.5 months (95% CI, 2.8-8.4) compared with the 5.6 months (95% CI, 2.8-8.4) observed in patients who did not receive bevacizumab (HR, 1.409; 95% CI, 0.814-2.437;P= .221).&nbsp;

Finally, in the small group of patients who were treated with an immune checkpoint inhibitor (n = 10), the median PFS was a short 1.7 to 2.3 months in patients who had single-agent treatment and 1.5 to 6.7 months in patients who had combination therapy.

To determine the PFS benefit of chemotherapy versus EGFR TKIs, data were analyzed for clinical and pathological characteristics and responses to systemic chemotherapeutic drugs, various targeted agents or immune checkpoint inhibitors.EGFRexon 20 mutations were tested using biopsy specimens from lung tumors, peripheral blood, or pleural fluid. Mutations were then identified using either polymerase chain reaction or next-generation sequencing.

Efficacy results were analyzed by Chi-Square test or Fisher&rsquo;s exact test, and to measure the PFS curves between the chemotherapy group and the EGFR TKIs group, investigators used the Kaplan-Meier method. To evaluate how PFS was impacted by several different variables, the Cox proportional hazards regression model was used. In addition, a log-rank test was utilized to determine significant differences.

Based on the results of the retrospective analysis, Guangjian Yang, MD, et al concluded that the currently approved EGFR TKIs are inferior to chemotherapy when given in the first- or second-line of treatment for advanced NSCLC. They also found that there are no EGFR TKIs that have activity in patients with CNS metastasis, which presents an unmet need.

Reference:

Yang g, Li J, Xu H, et al. EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: molecular heterogeneity and treatment outcome from nationwide real-world study [Published online March 13, 2020].Lung Cancer.doi: 10.1016/j.lungcan.2020.03.014.