Efficacy Data With Giredestrant Plus Everolimus in ER+/HER2– Breast Cancer: Erica L. Mayer, MD, MPH
Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute and Harvard Medical School, discussed primary efficacy data from the phase 3 evERA trial (NCT05306340), which is examining giredestrant in combination with everolimus (Afinitor) in patients with estrogen receptor–positive, HER2-negative advanced breast cancer previously exposed to a CDK4/6 inhibitor. The combination significantly improved progression-free survival (PFS) vs standard-of-care (SOC) endocrine therapy plus everolimus, with a median PFS of 8.77 months (95% CI, 6.60-9.59) vs 5.49 months (95% CI, 4.01-55.9), respectively, in the intention-to-treat population (HR, 0.56; P < .0001). The benefit was more pronounced in those with ESR1-mutant tumors, who experienced a median PFS of 9.99 months (95% CI, 8.08-12.94) vs 5.45 months (95% CI, 3.75-5.62) for SOC (HR, 0.38; P < .0001). She noted that the PFS advantage was observed regardless of the endocrine therapy backbone used in the control arm and that exploratory analyses suggested potential improvements in response rate and overall survival (OS) in certain subgroups.
Early Efficacy Data With Sevabertinib Monotherapy in HER2-Mutant NSCLC: Xiuning Le, MD, PhD
Xiuning Le, MD, PhD, of the University of Texas MD Anderson Cancer Center, unpacked data from the phase 1/2 SOHO-01 trial (NCT05099172) assessing sevabertinib monotherapy in patients with HER2-mutant advanced non–small cell lung cancer (NSCLC). Le reported that the oral irreversible HER2 inhibitor demonstrated robust and durable responses irrespective of previous lines of treatment. In previously treated patients (cohort D, n = 81), the objective response rate (ORR) was 64% (95% CI, 53%-75%), with a disease control rate of 81% (95% CI, 71%-89%). Treatment-naive patients (cohort F, n = 73) experienced an ORR of 71% (95% CI, 59%-81%). She concluded that these results position sevabertinib as a very promising new therapeutic option for patients with HER2-mutant lung cancer.
Optimal Patient Population to Receive Proton Therapy for Advanced NSCLC: Percy Lee, MD
Percy Lee, MD, of City of Hope, discussed the use of differentiated radiation modalities and stereotactic ablative radiotherapy (SABR) in patients with NSCLC. Lee noted that although most patients benefit from photon therapy, proton therapy is ideal for a special subset of patients where radiation delivery is challenging because of anatomy, tumor location, or size. He also highlighted the increasing complexity of re-irradiation, underscoring that appropriate timing and concurrent chemotherapy can improve outcomes. Additionally, Lee described SABR as a localized high-dose radiation approach that can control limited disease sites, potentially delaying systemic therapy or allowing for chemotherapy-free intervals.
OS Benefit With Osimertinib Plus Chemo by Poor Prognostic Factors in EGFR+ NSCLC: Pasi A. Jänne, MD, PhD
Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, discussed updated OS data from the phase 3 FLAURA2 trial (NCT04035486) evaluating osimertinib (Tagrisso) with or without carboplatin and pemetrexed in metastatic EGFR-mutated NSCLC. Jänne noted that the combination consistently improved OS vs single-agent osimertinib spanning prognostic subgroups, including those with central nervous system (CNS) metastases, EGFR exon 21 L858R mutations, plasma-detectable EGFR mutations, and TP53 alterations. Specifically, median OS was 40.9 months for those with CNS metastases who received the combination vs 29.7 months in those given osimertinib alone (HR, 0.72). He emphasized that no new safety signals were reported, supporting osimertinib plus chemotherapy as a first-line SOC in this population.