Real-world response and outcomes in NSCLC patients with EGFR exon 20 insertion mutations.

Abstract

9098 Background: There is currently no targeted therapy approved for patients with EGFR exon 20 insertion mutations (exon20ins) in NSCLC. Real world treatment outcome evidence for this rare population is limited. This study describes treatment patterns and outcomes in US patients with advanced NSCLC with EGFR exon20ins. Methods: The nationwide Flatiron Health electronic health record-derived deidentified database (cut-off 29 Feb 2020) was used to select 4 separate cohorts: (1) first-line (1L): patients receiving 1L therapy after documented exon20ins (1L start date as index date); (2) second or later line (≥2L): patients receiving ≥2L therapy after documented exon20ins (start date of ≥2L as index date); (3) ≥2L trial-aligned: ≥2L patients with baseline characteristics aligned with the key eligibility criteria of mobocertinib Trial NCT02716116 Part 3; and (4) ≥2L post platinum: ≥2L trial-aligned patients previously treated with platinum-based chemotherapy. Real-world endpoints were: confirmed overall response rate (cORR), PFS, and OS. Additional analyses were conducted for patients treated with immune-oncology therapy (IO). Results: Of 237 EGFR exon20ins patients, 129 patients were included in 1L cohort and 114 were in ≥2L cohort, including 63 ≥2L trial-aligned and 50 ≥2L post platinum patients. In 1L patients, EGFR TKI (28.7%) and platinum-based chemotherapy ± IO (56.6%) were the most common 1L regimens. In ≥2L patients, 28.1% received IO monotherapy, 17.5% received EGFR TKI, and 23.7% received platinum-based chemotherapy ± IO as index treatment. In the 1L setting, median PFS (mPFS) was 5.7 months for platinum-based chemotherapy and 4.5 months for IO + platinum-based chemotherapy. In the ≥2L setting, mPFS was 3.7 months for any therapy and 2.3 months for IO monotherapy. Full effectiveness data are provided in the accompanying table. Conclusions: This real world study provided a benchmark on the treatment outcome in patients with advanced NSCLC with EGFR exon20ins. Platinum-based chemotherapy was the most common 1L therapy and provided the longest mPFS. Immunotherapy, either as monotherapy or in combination with chemotherapy, appeared less effective for treatment of NSCLC with EGFR exon20ins. There is an unmet medical need for improved therapeutic options.[Table: see text]

Advanced non-small-cell lung cancer: how to manage EGFR and HER2 exon 20 insertion mutation-positive disease

“… 22 Moreover, adding immunotherapy to chemotherapy as a first-line combination did not improve the efficacy of chemotherapy. 22 …”

“…Platinum-based chemotherapy represents the most efficacious first-line treatment, with a median overall survival (OS) of 17 months and ORR of 19.5%. 22 Notably, immunotherapy evidenced dismal results either as a first-line or subsequent line of treatment. 22 Moreover, adding immunotherapy to chemotherapy as a first-line combination did not improve the efficacy of chemotherapy.…”

“… 22 Notably, immunotherapy evidenced dismal results either as a first-line or subsequent line of treatment. 22 Moreover, adding immunotherapy to chemotherapy as a first-line combination did not improve the efficacy of chemotherapy. 22 …”

“…22 Moreover, adding immunotherapy to chemotherapy as a first-line combination did not improve the efficacy of chemotherapy. 22 On this basis, there is a desperate need for new active treatments that might be beneficial for patients with Ex20ins NSCLC. Table 1 presents the relevant studies evaluating novel drugs in this context.…”

“…22 Notably, immunotherapy evidenced dismal results either as a first-line or subsequent line of treatment. 22 Moreover, adding immunotherapy to chemotherapy as a first-line combination did not improve the efficacy of chemotherapy. 22 On this basis, there is a desperate need for new active treatments that might be beneficial for patients with Ex20ins NSCLC.…”