Testing and treatment patterns in <i>KRAS</i> mutant mNSCLC: Results from the MYLUNG Consortium.

Abstract

e20639 Background: The Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic (MYLUNG) Consortium assesses biomarker testing patterns to improve testing rates and usage of targeted therapies for patients (pts) with non-small-cell lung cancer (NSCLC) in community practice. Evangelist et al. (2024) reported molecular testing rates and treatment patterns in pts with early-stage NSCLC. We now report metastatic (m)NSCLC cohort data, including rates of KRAS testing and use of KRAS G12C -targeted therapies, which are now approved in the 2L. Methods: Pts were enrolled from Dec2020-Sep2022 at 18 community practices (76 sites) across the US Oncology Network. Rates of next-generation sequencing (NGS), KRAS testing, use of KRAS -targeted therapy, and outcomes (ongoing) were assessed in the mNSCLC cohort as of 12Dec2024. Data collection continues for a 5-year follow-up. Results: This analysis includes 556 pts with mNSCLC, 90% of whom were newly diagnosed; median age 70y (37, 90); 51% female; 85% non-squamous histology; 81% current or former smoker. The overall rate of NGS testing improved from 37% in an earlier study (2018-2020) to 73% in this study. KRAS testing was done for 429 pts (77%) and 138 pts (32%) had a KRAS mutation. Of pts with KRAS mutations, the most common variants were G12C (46%), G12V (13%), and G12D (12%). Of pts with a G12C mutation, 47 pts (75%) had biomarker testing results before 1L treatment; of those, 6 pts received KRAS -targeted therapy. Only 15 pts with G12C mutations had 2L treatment but 73% got a KRAS -targeted therapy. The rate of advancement to 2L was similar for the G12C (30%) and total mNSCLC populations (33%). Median survival follow-up in the G12C cohort was 38mo (35, 43) with additional outcomes analysis ongoing. Conclusions: KRAS G12C mutations occurred in our study at an overall rate (15%) similar to previously reported rates. Of pts with a G12C mutation, 75% had biomarker test results before starting 1L treatment and 73% of G12C mutation pts got a KRAS -targeted therapy in the 2L. Notably, KRAS -targeted therapies were approved during our study, emphasizing the impact of testing programs for treatment planning. Real-world outcomes and the high rate of attrition before 2L treatment affirm the need for early testing in this population, as current research seeks to advance KRAS -targeted therapies to the 1L. Data from this and future studies will guide interventions to improve molecular testing rates in NSCLC. Clinical trial information: NCT05644808 . Treatment course of G12C -positive pts. KRAS G12C pts (N=63) 1L 2L No treatment (n, %) 7 (11) 41 (73) † Received treatment (n, %) 56 (89) 15 (27) † KRAS -targeted therapy ‡ 6 (11) § 11 (73) ¶ Other targeted therapy ‡ 0 (0) 2 (13) IO or IO+chemo ‡ 48 (86) 0 (0) Chemo ‡ 2 (3.6) 2 (13) † Denominator = Received 1L treatment. ‡ Denominator = Received treatment in 1L or 2L, respectively. § 5 pts on a clinical trial. 1 pt off-label. ¶ Treatment in 1L: IO (9), chemo (1), and IO+ KRAS inhibitor (1).