Maintenance Tucatinib-Based Therapy for HER2+ Breast Cancer: Erika P. Hamilton, MD
Erika P. Hamilton, MD, of Sarah Cannon Research Institute, highlighted the FDA approval of tucatinib (Tukysa) plus trastuzumab (Herceptin) and pertuzumab (Perjeta) as maintenance therapy following induction for adults with unresectable locally advanced or metastatic HER2-positive breast cancer. In the phase 3 HER2CLIMB-05 trial (NCT05132582), the regimen reduced the risk of disease progression or death by 35.9% vs placebo plus trastuzumab and pertuzumab (HR, 0.64; 95% CI, 0.51-0.80; P < .0001). Hamilton explained that HER2CLIMB-05 enrolled patients regardless of estrogen receptor (ER) status, whereas the palbociclib (Ibrance)–based regimen from the phase 3 PATINA trial (NCT02947685) is approved as maintenance only in ER-positive disease. She anticipated that the tucatinib regimen would be used primarily in ER-negative disease, noting that the phase 3 DESTINY-Breast09 trial (NCT04784715) of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab did not allow maintenance therapy. After T-DXd–based induction, Hamilton said she would treat to maximal response, which can take more than 1 year, before considering a switch to the HER2CLIMB-05 regimen
The Investigation of Novel CAR T-Cell Therapy Approaches in Myeloma: Binod Dhakal, MD, MS
Binod Dhakal, MD, MS, of the Medical College of Wisconsin, explored allogeneic and in vivo CAR T-cell therapy approaches designed to address the access, wait-time, lymphodepletion, and relapse challenges of the autologous products ciltacabtagene autoleucel (Carvykti) and idecabtagene vicleucel (Abecma) in multiple myeloma. In the phase 1 CaMMouflage trial (NCT05722418), the off-the-shelf BCMA-directed CAR T-cell therapy CB-011 produced an overall response rate (ORR) of 92% among 12 BCMA-naive patients treated at the selected dose; 83% achieved a complete response (CR) or better, and 91% of 11 evaluable patients achieved minimal residual disease (MRD) negativity. In an investigator-initiated phase 1 study (NCT06791681) of the in vivo agent ESO-T01, 4 of 5 heavily pretreated patients responded to a single infusion given without leukapheresis or lymphodepletion, and 3 achieved a stringent CR. In the phase 1 inMMyCAR study (NCT07075185), the in vivo agent KLN-1010 elicited an ORR of 100% across 3 dose levels (n = 18), and all 14 evaluable patients were MRD negative at a median follow-up of 2.8 months. Dhakal noted that durability, comparisons with autologous products, and long-term safety remained open questions.
The Differences Between Tumor-Informed and Tissue-Agnostic Assays in NSCLC: Young Kwang Chae, MD, MPH, MBA
Young Kwang Chae, MD, MPH, MBA, of Northwestern University Feinberg School of Medicine, outlined the differences between tumor-informed and tissue-agnostic MRD assays for postsurgical surveillance in non–small cell lung cancer. Tumor-informed assays were built from tissue obtained at surgery or biopsy to track a tumor-specific signature in the blood, which Chae said he tested every 3 months during surveillance. Tissue-agnostic assays relied on plasma alone, comparing cell-free DNA against germline DNA, single-nucleotide polymorphism libraries, and clonal hematopoiesis algorithms to identify tumor-derived DNA. Real-world data published by Chae and colleagues showed that both assay types were similarly effective at detecting prognostic MRD after lung cancer surgery, with each identifying cases the other missed. Because tissue is often exhausted by immunohistochemistry during the diagnostic workup, Chae said he sends both tests to avoid missing either signal.
Navigating Unanswered Questions in CLL Treatment Selection: Mary Ann Anderson, MBBS, FRACP, FRCPA, PhD
Mary Ann Anderson, MBBS, FRACP, FRCPA, PhD, of Royal Melbourne Hospital and Peter MacCallum Cancer Centre, addressed unresolved questions in treatment selection for chronic lymphocytic leukemia, emphasizing that care should be individualized for each patient. She noted that open decisions included continuous vs fixed-duration therapy, whether to add a monoclonal antibody to a continuous Bruton tyrosine kinase (BTK) inhibitor, which agents to use in fixed-duration regimens, whether to guide treatment by MRD, and how to sequence later-line therapy. Anderson said randomized phase 3 trials were unlikely to settle questions such as which BCL2 and BTK inhibitors to select, making collaborative group studies of real-world questions increasingly important. She pointed to the phase 3 CLL17 trial (NCT04608318), in which initial readouts at approximately 3 years suggested similar progression-free survival with continuous BTK inhibitor therapy and fixed-duration BCL2 inhibitor–based treatment, including among patients with high-risk genetic aberrations. Anderson noted that these data were still maturing.
