Welcome to this week’s edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw several breakthroughs in targeted therapies and FDA decisions, bringing renewed hope to patients and clinicians alike. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.
T-DXd Demonstrates Superior IDFS in HER2-Positive Early Breast Cancer
The phase 3 DESTINY-Breast05 trial has demonstrated that the antibody-drug conjugate trastuzumab deruxtecan (T-DXd; Enhertu) provides a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) compared with trastuzumab emtansine (T-DM1; Kadcyla).
This landmark finding pertains to patients with high-risk HER2-positive early breast cancer who still had residual invasive disease after completing neoadjuvant therapy. The superior outcomes suggest a potential shift in the adjuvant treatment paradigm for this patient population, who face an elevated risk of recurrence. Researchers believe T-DXd’s distinctive mechanism, including a cleavable linker and high drug-to-antibody ratio, confers a therapeutic advantage by enhancing the bystander effect to eradicate residual micrometastatic disease. The safety profile observed in the trial was consistent with known risks.
FDA Approves Lurbinectedin/Atezolizumab for ES-SCLC Maintenance
The FDA has approved the combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) as a first-line maintenance treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after initial chemotherapy and immunotherapy.
The approval is supported by the phase 3 IMforte trial, which showed the combination significantly improved both progression-free survival (PFS) and overall survival (OS) compared with atezolizumab monotherapy. The combination reduced the risk of disease progression or death by 46% and the risk of death by 27%. This positive result addresses the critical need for a proactive maintenance strategy in this aggressive cancer to prevent rapid relapse.
Deciding When and How to Add Therapy for Steroid-Refractory GVHD
In a live discussion, Michael R. Bishop, MD, discusses the management of steroid-refractory chronic graft-vs-host disease (GVHD), emphasizing the need for early intervention to improve patient outcomes and prevent organ progression. Since increasing steroid dosage is often ineffective, patients who fail to respond to initial systemic corticosteroids meet the criteria for steroid refractoriness and should immediately move to a second-line agent.
Available FDA-approved options include ruxolitinib (Rituxan), ibrutinib (Imbruvica), belumosudil (Rezurock), and axatilimab (Niktimvo). Data from the ROCKstar trial highlights the efficacy of belumosudil, which achieved a high overall response rate, allowed for successful steroid taper in nearly two-thirds of patients, and demonstrated notable organ-specific responses, particularly in joint/fascia and lower gastrointestinal GVHD.
Final Data Show Continued Responses, Safety by Mitazalimab in Pancreatic Cancer
The final 30-month data from the phase 1b/2 OPTIMIZE-1 trial show that mitazalimab, a CD40 agonistic antibody, combined with mFOLFIRINOX chemotherapy, demonstrates continued promising efficacy and a manageable safety profile in patients with metastatic pancreatic cancer.
The agent met its primary end point with a final objective response rate (ORR) of 54.4% and a median duration of response of 12.6 months. Key survival data highlights include a median OS of 14.9 months and a 30-month OS rate of 21%. These durable results in a difficult-to-treat cancer underscore the therapy’s potential and support its advancement to a pivotal phase 3 trial.
FDA Approves Guardant 360 CDx With Imlunestrant in ESR1+ Breast Cancer
The FDA has approved the Guardant360 CDx as a companion diagnostic to identify ESR1 mutations in patients with estrogen receptor (ER)-positive, HER2-negative advanced or metastatic breast cancer. This approval is linked to the use of the oral selective estrogen receptor degrader (SERD), imlunestrant (Inluriyo).
Data from the EMBER-3 trial demonstrated that imlunestrant reduced the risk of disease progression or death by 38% in patients with ESR1-mutated disease compared to standard endocrine therapy. The test allows physicians to use a simple blood draw for comprehensive genomic profiling, ensuring that patients with this specific mutation receive the appropriate targeted treatment.