ASCO 2024 - Advances in NSCLC Treatments

The 2024 ASCO Annual Meeting spotlighted several groundbreaking developments in managing non-small cell lung cancer (NSCLC), particularly focusing on targeted therapies for specific genomic alterations that drive cancer progression. A summary of key highlights follows:

1. EGFR-mutant NSCLC (Phase 3 LAURA Trial1): Osimertinib showcased significant efficacy in unresectable stage III EGFR-mutant NSCLC post-definitive chemoradi therapy. Impressively, the drug extended median progression-free survival (PFS) to 39.1 months compared to 5.6 months in the control group, as reviewed by the blinded independent central review (BICR).
2. HER2-mutant NSCLC (Phase 2 DESTINY-Lung02 and Beamion LUNG-1 Trials2-3): The DESTINY-Lung02 trial reported that T-DXd showed an objective response rate of 50% and a median PFS of 10 months in patients who had progressed after previous treatments, underscoring its promising anti-tumor activity. Moreover, a novel HER2 tyrosine kinase inhibitor (TKI), zongertinib, demonstrated encouraging preliminary  efficacy in the Beamion LUNG-1 trial for pre-treated patients harboring HER2 tyrosine kinase domain (TKD) mutations.‍
3. EGFR Exon 20 Insertions (Phase 2 WU-KONG1 Study4): Sunvozertinib demonstrated substantial efficacy in patients who had progressed after previous therapies, including amivantamab (13.1%). The best overall response rate was 53.3%, regardless of prior amivantamab treatment. ‍
4. KRAS G12C-mutant NSCLC (Phase 3 KRYSTAL-12 Trial5): Adagrasib demonstrated a significantly improved median PFS of 5.5 months compared to 3.8 months with docetaxel treatment for patients who have progressed after prior chemotherapy and immunotherapy.‍
5. ALK-positive NSCLC (Phase 3 CROWN Trial6): According to the 5-year analysis, lorlatinib continues to perform superior against crizotinib.The median PFS has still not been reached60% PFS rate) and is the longest PFS reported in advanced ALK-positive NSCLC.

These findings underscore the pivotal role of genetic profiling in NSCLC to tailor and enhance treatment efficacy, promising improved patient outcomes across various mutation-driven subtypes.

Reference:

1. Suresh S. Ramalingam et al. presented at the 2024 ASCO annual meeting. Osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFR-mutated NSCLC: primary results of the Phase 3 LAURA study.
2. Pasi A. Janne et al. presented at the 2024 ASCO annual meeting. Trastuzumab deruxtecan (T-DXd) in patients with HER2-mutant metastatic non–small cell lung cancer (mNSCLC) Final analysis results of DESTINY-Lung02.
3. John Heymach et al. presented at the 2024 ASCO annual meeting. Phase Ia/Ib trial of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor (TKI), in patients (pts) with HER2 aberration-positive solid tumors: Updated Phase Ia data from Beamion LUNG-1, including progression-free survival (PFS) data.
4. James Chih-Hsin Yang et al. presented at the 2024 ASCO annual meeting. A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study.
5. Tony S. K. Mok et al. presented at the 2024 ASCO annual meeting. KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRAS G12C mutation.
6. Benjamin J. Solomon et al. presented at the 2024 ASCO annual meeting. Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study.

‍