The Targeted Pulse: FDA Approvals and Clinical Insights

Welcome to this week's edition of The Targeted Pulse. This week in oncology, we saw a number of significant developments, from FDA approvals to promising clinical trial data for various cancer types. Here is a summary of the top stories.

FDA Approves Subcutaneous Pembrolizumab for Solid Tumor Indications

The FDA has approved a new subcutaneous (SC) formulation of pembrolizumab (Keytruda Qlex), co-formulated with berahyaluronidase alfa, covering all solid tumor indications previously approved for the intravenous (IV) delivery.

The approval follows the pivotal phase 3 3475A-D77 trial in metastatic non-small cell lung cancer, which successfully demonstrated noninferior pharmacokinetics and consistent efficacy and safety profiles compared to the IV version. A major benefit of the SC injection is a significant reduction in treatment time; the study found it reduced a patient's time in-chair and in the treatment room by nearly 50% and cut healthcare practitioners' active time by over 45%. This new method is expected to improve treatment efficiency and the overall experience for patients and clinics.

Giredestrant Improves PFS in ER+, HER2– Breast Cancer

The phase 3 evERA study demonstrated that the oral selective estrogen receptor degrader (SERD), giredestrant, combined with everolimus significantly improved progression-free survival (PFS) in patients with estrogen receptor-positive, HER2-negative, locally advanced or metastatic breast cancer. The regimen met both co-primary end points in the overall population and the ESR1-mutant population. The trial is the first positive head-to-head phase 3 study evaluating an all-oral SERD-containing combination versus a standard-of-care combination in this setting. This breakthrough offers a promising new oral treatment avenue for patients whose disease has progressed following a CDK inhibitor.

Clinical Factors and Transplantation Are Associated With PCL Prognosis

A retrospective study on plasma cell leukemia (PCL), a rare and aggressive blood cancer, revealed significant survival disparities and treatment associations. Patients with secondary PCL (sPCL) had a markedly worse prognosis, with a median overall survival (OS) of 3.2 months, compared to 36.6 months for those with primary PCL (pPCL). Critically, the study found that receiving a hematopoietic stem cell transplantation was strongly associated with improved survival across both subtypes, boosting median OS to 48.7 months for the entire transplanted cohort, compared to 5.9 months for those who did not receive one. These findings underscore the importance of transplantation for PCL, especially pPCL, and highlight the need for better treatments for sPCL.

Updated NCCN Guidelines Add Lurbinectedin Maintenance in ES-SCLC

The updated NCCN Clinical Practice Guidelines for extensive-stage small cell lung cancer (ES-SCLC) now include a new first-line maintenance option: lurbinectedin (Zepzelca) combined with atezolizumab (Tecentriq). This change is based on the Phase 3 IMforte trial data, which demonstrated a significant survival benefit for the doublet therapy. The combination more than doubled the median progression-free survival (PFS) to 5.4 months (vs. 2.1 months with monotherapy) and provided a clinically meaningful improvement in overall survival. This new regimen is recommended for patients who achieve at least stable disease after initial chemoimmunotherapy.

Exploring Genetics and Advanced Therapies in Prostate Cancer

In recognition of Prostate Cancer Awareness Month, Daniel Petrylak, MD, highlighted key advancements in the field, emphasizing the importance of identifying genetic mutations, particularly BRCA and related DNA repair deficiencies.

He notes this finding has therapeutic and familial implications. For patients, it establishes DNA repair as a target for metastatic disease, supporting the use of PARP inhibitors and their potential synergy with antiandrogens in earlier hormone-sensitive settings. Familially, it necessitates proper genetic counseling for family members to screen for associated cancers like breast, ovarian, and pancreatic. Dr Petrylak also advocates for an intensified upfront treatment approach for metastatic prostate cancer by adding antiandrogens to the standard androgen deprivation therapy.