The Targeted Pulse: Excellent Advancements in Breast Cancer Management and an Extended Access Program for NMIBC

TMLI Plus Post-Transplant Cyclophosphamide Improves Transplant Outcomes in AML

Administering total marrow and lymphoid irradiation at 20 Gy alongside post-transplant cyclophosphamide improved outcomes for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. These findings from a phase 1 trial (NCT03467386) were presented at the 2025 Tandem Meetings. In this article, Anthony S. Stein, MD, professor and co-director of the Acute Leukemia Program at City of Hope in Duarte, California, provides deeper insight into the trial design and key findings in an interview with Targeted Oncology^TM.

“The key takeaway is that, in the past, transplant has always been thought of as having a high risk of toxicity, morbidity, and mortality,” Stein explained. “At least in this study, we can show that, up to the present time, no patients have died from the transplant regimen or from chronic graft-vs-host disease. I did not mention earlier, but we can also show that the majority—in fact, all our patients—have been able to discontinue immunosuppression.” To gain more perspective, access the full interview here.

Significant PFS Benefit Is Achieved With Elacestrant in ER+, HER2– Breast Cancer

Elacestrant (Orserdu) improved progression-free survival (PFS) compared with standard therapy with an aromatase inhibitor or fulvestrant (Faslodex) in patients with pretreated, estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer, regardless of ESR1 variant allele fraction (VAF) level. These findings from a post hoc subgroup analysis of the phase 3 EMERALD trial (NCT03778931) were presented during the 42nd Annual Miami Breast Cancer Conference.

“In patients with longer prior endocrine therapy and CDK4/6 inhibition, both ESR1 and PIK3CA mutations are known to be drivers of cancer growth, but even at a low VAF, ESR1 mutations become clinically significant,” Aditya Bardia, MD, MPH, FASCO, and coauthors, stated in the presented poster. “In the context of ESR1 and PIK3CA mutations, elacestrant was associated with an improvement in median PFS vs the standard of care in ER-positive, HER2-negative metastatic breast cancer, regardless of the type of ESR1 mutation variant and the level of VAF.” Bardia is lead study author and professor in the Department of Medicine, Division of Hematology/Oncology at UCLA Health’s Jonsson Comprehensive Cancer Center in Los Angeles, California. For more information on the trial data, access the full article here.

Real-World Data Show HER2DX Effectively Guides Treatment in HER2+ Breast Cancer

The HER2DX genomic assay is an effective tool designed to guide treatment decisions for patients with stage I to III HER2-positive breast cancer. In a prospective real-world study analyzing data from November 2021 to September 2024 and consisting of 297 patients across 12 hospitals in Spain, the HER2DX assay supported treatment reduction decisions without compromising outcomes. In addition, the assay accurately predicted pathologic complete response.

“The capacity to forecast a patient’s therapeutic response prior to treatment initiation allows oncologists to adjust treatment intensity appropriately, effectively reducing unnecessary toxicity and healthcare costs,” said Antonio Llombart-Cussac, MD, PhD, head of the medical oncology department at Hospital Arnau de Vilanova in Valencia, Spain and investigator of the study, in the press release. For complete trial data, access the full article here.

OSE2101 Plus FOLFIRI Achieves 1-Year OS in Advanced or Metastatic PDAC

OSE2101 (Tedopi) in combination with FOLFIRI (irinotecan, leucovorin, and 5‐fluorouracil) chemotherapy achieved a 1-year overall survival rate in patients with advanced or metastatic pancreatic ductal adenocarcinoma, meeting the primary end point of the randomized, non-comparative phase 2 TEDOPAM trial (NCT03806309). The trial evaluated OSE2101 alone or in combination with nivolumab (Opdivo), followed by FOLFIRI reintroduction, vs FOLFIRI as maintenance therapy. OSE2101 is a neoepitope-based therapeutic cancer vaccine designed to target tumor-associated antigens in HLA-A2–positive cancers.

“These are positive results in a non-comparative trial. That said, we need to better understand the contribution of Tedopi in the context of this combination. A large translational program on tumor tissue, blood, and imaging is ongoing. Additional analysis at a longer time point will also be necessary for more mature survival data,” explained Cindy Neuzillet, MD, PhD, Curie cancer research Institute, Saint-Cloud, France, and principal investigator of the TEDOPAM study, in a press release. For more information on trial data, access the full article here.

Expanded Access Program for Cretostimogene Grenadenorepvec in NMIBC

An expanded access program (EAP) evaluating cretostimogene grenadenorepvec in patients with BCG-unresponsive, high-risk non–muscle-invasive bladder cancer is currently enrolling patients, as discussed in a presentation at the 25th Annual Meeting of the Society of Urologic Oncology. The EAP is a “creative approach to generating needed real-world data on how the drug performs in a pragmatic cohort that reflects what we see in practice,” explained Sarah P. Psutka, MD, MSc, during the presentation. Preliminary findings from the ongoing BOND-003 trial (NCT04452591) were also presented, demonstrating that the agent is efficacious and well tolerated; however, these data are primarily from a White male population, highlighting the need for greater diversity to gain broader insights, Psutka explained.

“With the EAP, it is an opportunity for patients to receive the drug in real-world practice. The company is working to recruit sites that are likely to have a fairly diverse patient population—academic centers but also community practices and even VAs [US Department of Veterans Affairs practices]—with the goal of being able to offer patients who might not be able to access FDA-approved treatments in this disease space a drug that has good oncologic efficacy, a great safety profile, and a good tolerability profile,” said Sarah P. Psutka, MD, MSc, associate professor of urology at the University of Washington and Fred Hutchinson Cancer Center in Seattle, Washington. For further enrollment information, access the full article here.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

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