Aumolertinib Shows Promise in NSCLC, Ivonescimab Outperforms Pembrolizumab, and Novel Therapies Emerge in Breast Cancer and Multiple Myeloma
核心洞察
Aumolertinib (搜索) demonstrated improved progression-free survival in unresectable stage III EGFR (搜索)-mutated NSCLC (搜索) patients post-chemoradiation therapy in the phase 3 POLESTAR trial.
Ivonescimab reduced the risk of disease progression or death in PD-L1-positive advanced NSCLC (搜索) compared to pembrolizumab in the phase 3 HARMONi-2 trial.
Oral SERDs and PROTACs are providing additional treatment options for breast cancer (搜索), especially in the post-CDK4/6 inhibitor setting, according to Erika Hamilton, MD.
Aumolertinib (搜索) (formerly almonertinib; HS-10296) has shown promising results in patients with unresectable stage III non-small cell lung cancer (搜索) (NSCLC (搜索)), according to an interim analysis of the phase 3 POLESTAR trial (NCT04951635). The trial, presented at the 2024 International Association for the Study of Lung Cancer World Conference on Lung Cancer (WCLC), indicated an improvement in progression-free survival for patients receiving aumolertinib after chemoradiation therapy (CRT). Patients were randomly assigned 2:1 to receive 110 mg of aumolertinib once daily or a matching placebo. However, the experimental arm experienced an increase in any-grade adverse events (AEs), leading to treatment interruptions, dose reductions, and discontinuations, including elevated blood creatinine phosphokinase levels, radiation pneumonitis, and decreased white blood cell count. "These findings demonstrate aumolertinib [is] a novel treatment option for patients with unresectable stage III EGFR (搜索)-mutated NSCLC after CRT," said lead study author Xiangjiao Meng, MD, of Shandong Cancer Hospital and Institute at Shandong First Medical University in Jinan, China.
Ivonescimab vs. Pembrolizumab in Advanced NSCLC
Data from the primary analysis of the phase 3 HARMONi-2 trial (NCT05499390) indicated that ivonescimab reduced the risk of disease progression or death in PD-L1–positive advanced NSCLC (搜索) compared with pembrolizumab (Keytruda). The findings from the HARMONi-5 trial (NCT04900363) supported the design of the double-blind HARMONi-2 trial, which included 398 patients who were randomly assigned 1:1 to receive 20 mg/kg of ivonescimab every 3 weeks or 200 mg of pembrolizumab every 3 weeks. "This is the first randomized phase 3 study to demonstrate a clinically significant improvement in efficacy with a novel drug compared with pembrolizumab in advanced NSCLC," said Caicun Zhou, MD, PhD, lead study author and director of the Department of Oncology at Shanghai Pulmonary Hospital in China.
Advancements in Breast Cancer Treatment
The treatment landscape for endocrine therapies in breast cancer (搜索) is rapidly evolving, with oral selective estrogen receptor degraders (SERDs) and proteolysis-targeting chimeras (PROTACs) providing additional treatment options, especially in the post-CDK4/6 inhibitor setting. Erika Hamilton, MD, director of breast cancer research at the Sarah Cannon Research Institute, highlighted several ongoing trials, including phase 1 trials evaluating ARV-471 both as a monotherapy and in combination with palbociclib (Ibrance). "There are adjuvant trials for curative breast cancer [treatment] that may replace our traditional endocrine backbones. These trials come in 2 varieties: comparing the new agents up front with aromatase inhibitors and using a switch strategy after 2 to 5 years on an aromatase inhibitor. With all these trials ongoing, we will certainly have a rich dataset to improve our endocrine therapies," Hamilton explained.
CAR T-Cell Therapy in Multiple Myeloma
In relapsed multiple myeloma (搜索), chimeric antigen receptor (CAR) T-cell therapy is emerging as a promising option. Saad Z. Usmani, MD, FACP, MBA, a myeloma specialist & cellular therapist at Memorial Sloan Kettering Cancer Center, reviewed the case of a 60-year-old woman diagnosed with Revised International Staging System (R-ISS) stage II/R2-ISS stage III IgGκ relapsed multiple myeloma. He discussed third-line CAR T-cell therapy options, highlighting data from the KarMMa-3 (NCT03651128) trial and addressed the management of AEs associated with ide-cel (idecabtagene vicleucel; Abecma), including cytokine release syndrome (CRS). "You are giving these revved up T cells to patients and asking them to become hyperactive as soon as they are exposed to that specific surface marker or antigen. So of course they are going to become active, release cytokines, and essentially make the patient feel like they have a bad flu. That is what, essentially, CRS is. When we were using CAR T cells 10 to 12 years ago, there was a concern that if you try to stop that process, you may not get the efficacy. But pretty soon we learned that if we let that go too long, patients may even die from it," Usmani explained.
BCL-2 Inhibitors in Preventing Apoptosis
According to John Seymour, MD, director of hematology at the Peter MacCallum Cancer Center (搜索) and the Royal Melbourne Hospital, BCL-2 inhibitors are a key component to preventing apoptosis, or programmed cell death. Seymour discussed the emergence of combining BCL-2 inhibitors with Bruton tyrosine kinase (BTK) inhibitors or anti-CD20 antibodies to improve outcomes and reduce the probability of resistance. "Another key finding was that with continued single-agent therapy, there is a significant risk of induction of resistance mutations that lead to outgrowth of resistant clones. That was the impetus to use combination therapy, either with BTK inhibitors or with an anti-CD20 antibody, to achieve deeper reductions but enable time-limited therapy. The third paradigm that emerged was, if we use this time-limited therapy, it then retains disease sensitivity, so at progression, we can retreat with that same combination," Seymour explained.