The studies summarized below were reported online over the past month in The ASCO Post, generating a high number of visitors. For comprehensive reviews of these studies and more, visit ASCOPost.com.
Trastuzumab Duocarmazine in Previously Treated HER2-Positive Metastatic Breast Cancer
In the phase III TULIP trial published in the Journal of Clinical Oncology, Turner et al evaluated a third-generation HER2-targeted antibody-drug conjugate, trastuzumab duocarmazine (T-Duo), in patients with advanced or metastatic HER2-positive breast cancer. A total of 437 patients were randomly assigned to receive T-Duo or a physician’s choice of treatment. The primary endpoint, progression-free survival, was significantly improved in the T-Duo group, with a median progression-free survival of 7 months compared to 5 months in the physician’s choice group (hazard ratio [HR] = 0.64, P = .002).
T-Duo also showed a trend toward better overall survival (20 vs 16 months), although this was not statistically significant (P = .153). The objective response rate was similar in both groups, but the duration of response was longer in the T-Duo group (15 vs 5 months). Ocular toxicity was a notable side effect of T-Duo, leading to discontinuations in 35.4% of patients, primarily due to keratitis and conjunctivitis. Despite these adverse events, the study concluded that T-Duo significantly reduced progression risk in this patient population.
Nivolumab Plus Ipilimumab in Aggressive Thyroid Carcinoma
In a phase II study published in JAMA Oncology, Sehgal et al assessed the combination of nivolumab and ipilimumab in patients with aggressive thyroid carcinoma. The trial involved 49 patients at Dana-Farber Cancer Institute, including those with radioiodine-refractory differentiated thyroid carcinoma, medullary thyroid carcinoma, and anaplastic thyroid carcinoma. Patients received nivolumab (3 mg/kg every 2 weeks) and ipilimumab (1 mg/kg every 6 weeks) until disease progression or intolerable side effects.
The primary outcome was objective response in patients with radioiodine-refractory differentiated thyroid carcinoma, among whom only 9.4% (3/32) had a partial response—below the predefined efficacy threshold. However, the clinical benefit rate was 62.5% in the differentiated thyroid carcinoma group, including 83.3% in those with oncocytic carcinoma. Among patients with anaplastic thyroid carcinoma, 30% had objective responses, and 50% experienced clinical benefit. No responses were observed in the medullary thyroid carcinoma cohort, which had a 28.6% clinical benefit rate.
The study also found that NRAS variants were associated with poorer survival outcomes. Treatment-related adverse events occurred in 28.5% of patients, but no treatment-related deaths were reported. The investigators concluded that although nivolumab and ipilimumab showed activity in anaplastic thyroid carcinoma, the results were insufficient to justify further exploration in non–biomarker-selected differentiated thyroid carcinoma.
Brexucabtagene Autoleucel as Standard Therapy for Adults With Relapsed/Refractory B-Cell ALL
In an analysis published in the Journal of Clinical Oncology, Roloff et al assessed the use of the CD19-directed CAR T-cell therapy brexucabtagene autoleucel as a standard treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). The study, which involved 31 U.S. centers, included data from 204 patients, with 189 receiving the treatment. The median follow-up was 11.4 months. Notably, 42% of patients received treatment in morphologic remission.
Among 168 evaluable patients, 90% achieved complete remission, with 79% of those testing measurable residual disease (MRD)-negative. The median progression-free survival was 9.5 months, with 6- and 12-month progression-free survival rates of 59% and 48%. Median overall survival was not reached, but 6- and 12-month overall survival rates were 78% and 63%, respectively. Patients who received consolidative hematopoietic cell transplantation (HCT) after brexucabtagene autoleucel had significantly improved progression-free survival compared to those who did not (HR = 0.34).
Nevertheless, the therapy was associated with significant toxicities, including grade 3 or 4 cytokine-release syndrome (11%) and immune effector cell–associated neurotoxicity syndrome (31%). Ten patients (5.3%) died from toxicity or infection. The study confirmed high MRD-negative remission rates, similar to ZUMA-3, and highlighted the benefit of HCT consolidation.
Addition of Atezolizumab Plus Bevacizumab to Chemotherapy in Advanced Biliary Tract Cancer
In the phase II IMbrave151 trial, reported in Journal of Clinical Oncology, Macarulla et al evaluated the combination of atezolizumab and bevacizumab plus chemotherapy (cisplatin and gemcitabine) as a first-line treatment for advanced biliary tract cancer. The trial included 162 patients, who were randomly assigned to receive either atezolizumab plus bevacizumab (n = 79) or atezolizumab plus placebo (n = 83), alongside chemotherapy, for up to eight cycles. The primary endpoint was progression-free survival.
The results showed a median progression-free survival of 8.3 months for the atezolizumab/bevacizumab group compared to 7.9 months in the placebo group (HR = 0.67). The progression-free survival rates at 6 and 12 months were 78% vs 63% and 33% vs 20%, respectively. In an exploratory analysis, high VEGFA gene expression was linked to a more substantial progression-free survival benefit in the atezolizumab/bevacizumab group (HR = 0.44). However, median overall survival was similar between the groups (14.9 vs. 14.6 months).
Adverse events were common, with 74% of patients in both groups experiencing grade 3 or 4 events. The study concluded that the addition of bevacizumab to atezolizumab did not affect overall survival, and high VEGFA expression may serve as a predictive biomarker for treatment benefit.
For more clinical oncology news, visit ASCOPost.com.
