Chemotherapy Regimens Remain Key to Survival in Post EGFR-TKI NSCLC Harboring EGFR Mutations

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Chemotherapy regimens have been known to produce favorable outcomes among patients with EGFR-mutated non–small cell lung cancer (NSCLC) after progression on EGFR-tyrosine kinase inhibitor (TKI).¹

According to a multicohort study, median progression-free survival (PFS) was not significantly different between first-line chemotherapy regimens (P = .50). The highest PFS was seen with platinum-based chemotherapy plus pemetrexed (PP) at 5.2 months (95% CI, 4.5-5.9) and the combination of carboplatin, paclitaxel, bevacizumab (Avastin), and atezolizumab (Tecentiq; CPBA) at 5.9 months (95% CI, 3.8-80).

Patients with EGFR-mutated NSCLC who were treated with chemotherapy regimens containing paclitaxel or pemetrexed after progression on an EGFR-TKI were identified in 2 tertiary centers in the Netherlands and eligible for inclusion in the study.

There were 135 patients eligible for inclusion. Ninety-six (71.1%) patients had previously received treatment with osimertinib (Tagrisso) upfront (n = 8) or after prior first- or second-generation EGFR-TKI (n = 88), and 33 patients received more than 1 line of chemotherapy.

A total of 171 lines of chemotherapy were identified, including PP (n = 95), CPBA (n = 32), paclitaxel/bevacizumab (PB, n = 36), and carboplatin/paclitaxel/bevacizumab (CPB, n = 8). There were 106 lines from the 171 given as first-line after EGFR-TKI, of which the majority (n = 76, 71.7%) were PP, followed by CPBA (n = 22, 20.8%).

Among patients, the baseline characteristics of the first-line cohort showed that the median age was 63 years (range, 33-80), most patients were female (61.3%), and most had never smoked (57.5%). Additionally, the majority of patients in this cohort harbored EGFR exon 19 deletions (51.9%) and EGFR exon 21 L858R mutations (30.2%) and had a concomitant TP53 aberration at baseline (67.0%).

At time of data cutoff, the median follow-up was 48.4 months (95% CI, 31.5-65.4) in the in the first-line cohort, and there were 105 events of progression, and 93 deaths. Treatment discontinuation resulting from toxicity was highest in the PB cohort (41.6%). This was followed by PP (21.1%), and CPBA (12.5%). No patients in the CPB cohort discontinued treatment due to toxicities.

In the first-line cohort, the median PFS was 5.4 months (95% CI, 4.7-6.1). This did not differ between the different types of EGFR mutations (p = .59), as well as between those with or without concomitant TP53 mutations (p = .11). In patients with CNS metastases in the first-line cohort, the median PFS was similar between those given PP at 4.8 months (95% CI, 2.3-7.3), and those given CPBA at 3.8 months (95% CI, 0.5-7.5; p = .67). In this cohort, 44 patients (41.5%) experienced durable benefits, and patients with durable benefit had less known CNS metastasis prior to start of chemotherapy compared with patients without durable benefit (20.5% v 43.5%; p = 0.01). Additionally, most patients given PB (n = 32) were given the regimen in a second- or later line and had a median PFS of 4.9 months (95% CI, 3.3-6.6).

The median OS for the first-line regimens was 15.3 months (95% CI, 11.60-18.9), and there was no significant difference between regimens (p = .85). Among patients with CNS metastases, the median OS was longer for patients given PP at 11.8 months (95% CI, 7.5-16.1) vs CPBA at 8.7 months (95% CI, 6.9-10.4). However, these findings did not meet statistical significance (p = .08).

Further, the ORR and DCR were not significantly different between the first-line regimens (p = .27 v p = .59, respectively). However, ORR differed significantly between the treatment regimens (p = .02), as PP had the worse ORR at 40.0% (95% CI, 30.1-50.6).

In the PB cohort, most patients (88.9%) were given the regimen as a second- or later line of treatment. Their median PFS of 4.9 months (95% CI, 3.3-6.6), and 9 patients who experienced disease progression as best overall response on PP, subsequently received PB. Seven of the 9 patients (77.8%) achieved disease control with the PB regimen, 1 patient showed stable disease and had a PFS of 8.2 months, and 6 patients had a partial response with a PFS ranging from 3.2-8.3 months.

Overall, each of these chemotherapy regimens provided a survival benefit after treatment with an EGFR-TKI, and the most effective regimen has yet to be determined.

_REFERENCE:

_{Steendam CMJ, Ernst SM, Badrising SK, et al. Chemotherapy for patients with EGFR-mutated NSCLC after progression on EGFR-TKI's: Exploration of efficacy of unselected treatment in a multicenter cohort study. Lung Cancer. 2023;181:107248. doi:10.1016/j.lungcan.2023.107248}