Journal of Clinical Oncology

8521 Background: The central nervous system (CNS), particularly after progression on third-generation EGFR TKIs, represents a common yet challenging scenario. While recent trials establish amivantamab-lazertinib for EGFR-mutant NSCLC, their real-world applicability is limited by patient complexity and access barriers, highlighting an urgent need for flexible, real-world solutions. Methods: To eva…

e12507 Background: The addition of pembrolizumab (PEM) to neoadjuvant chemotherapy (NAC) has been shown to significantly improve pathological complete response (pCR) rates in patients with early-stage triple-negative breast cancer (TNBC). However, long-term prognostic outcomes in real-world clinical practice, specifically for patients who achieve pCR, have not been sufficiently verified. This stu…

8093 Background: Both atezolizumab (atezo) and durvalumab (durva) are preferred first-line (1L) systemic treatment options for extensive-stage small cell lung cancer (ES-SCLC) with similar efficacy in the IMpower133 and CASPIAN phase 3 trials. There is limited evidence comparing their survival outcomes in the real-world (rw) setting. This study described rw overall survival (rwOS) in patients (pt…

e12532 Background: Adjuvant CDK4/6 inhibitors benefit selected HR+/HER2− early breast cancer (EBC), yet monarchE (high-risk node-positive) and NATALEE (broader stage II–III, including high-risk N0) define eligibility differently. Real-world applicability across treatment settings is unclear. Methods: Retrospective study of consecutive stage I–III HR+/HER2−/low EBC treated at KFMC (Jan-2021–Dec-20…

e12561 Background: Exosomal RNA captures dynamic tumor biology and may overcome limitations of tissue biopsy and imaging, which, in the breast cancer segment, provide high false positivity and overdiagnosis (10-40%) and limitations with dense breast tissue with screening mammography and no reliable blood biomarkers for early recurrence or post-surgical risk stratification. A minimally invasive, r…

8582 Background: Human leukocyte antigen class I (HLA-I) molecules are essential for neoantigen presentation and T cell recognition, yet the clinical significance of allelic imbalance within HLA-I genes (HLA-AI) in immune checkpoint inhibitors (ICIs) therapy remains undefined. Methods: Here, we established haplotype-specific, coverage-based (cHLA-AI) compatible with routine biopsy-derived sequenc…

9518 Background: Advanced melanoma has a high mortality rate; however, survival for patients (pts) treated with anti–PD-1–based therapy tends to plateau at 3–4 years, suggesting that pts alive at 3 years are likely to have prolonged benefit. This highlights the need for novel therapies that offer increased survival beyond 3-4 years. RP1 (vusolimogene oderparepvec) is an HSV-1–based oncolytic immu…

7096 Background: Mogamulizumab, monoclonal antibody against CCR4, is approved for relapsed/refractory cutaneous T cell lymphoma (CTCL), with an overall response rate of 28%in CTCL. The most common toxicity is mogamulizumab-associated rash (MAR), occurring in ~24% of patients and reported in up to 88% of responders, frequently leading to treatment discontinuation. Given the limited therapeutic opt…

8561 Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced non-small cell lung cancer (NSCLC), enabling durable responses in a subset of patients (pts). However, detailed clinical trajectories and patterns of late disease progression among long-term survivors remain poorly characterized. Methods: This multicenter retrospective cohort study enrolled advanced NSCLC p…

e12571 Background: Breast cancer remains a leading cause of cancer-related morbidity worldwide, with imaging central to early diagnosis and treatment planning. Ultrasonography is widely used due to its safety and effectiveness in dense breast tissue; however, interpretation is operator dependent and varies across clinical settings. Although deep learning has advanced ultrasound-based cancer detec…

8017 Background: Circulating tumor DNA (ctDNA) is a promising biomarker for detecting molecular residual disease (MRD) and predicting recurrence after curative treatment in non-small cell lung cancer (NSCLC). Ultrasensitive personalized assays have demonstrated clinical validity at detection thresholds of ~80-100 parts per million (PPM). As this assay can detect ctDNA at concentrations an order o…

9577 Background: Circulating tumor DNA (ctDNA) is a novel biomarker for detecting molecular residual disease (MRD) and monitoring recurrence risk in melanoma. Personalized, tumor-informed ctDNA assays may enable highly sensitive and specific longitudinal detection of disease burden following curative-intent surgery. Here, we evaluate the prognostic value of whole-genome sequencing (WGS)-based ctD…

8608 Background: KRAS-G12C mutations are found in ~12% of mNSCLC. KRAS-G12C inhibitors sotorasib and adagrasib are approved treatments but have never been compared head-to-head. We report the first large, multi-institutional database analysis comparing efficacy and safety of sotarasib vs adagrasib. Methods: Flatiron Health's de-identified electronic health record US database was used to identify …

e12534 Background: In hormone receptor-positive, HER2-negative early-stage breast cancer (HR+/HER2- EBC), the biological characteristics and therapeutic response to endocrine treatment are fundamentally shaped by the synergistic interplay between estrogen receptor (ER) and progesterone receptor (PR). Nevertheless, the role of discordant expression levels between ER and PR—termed ΔER-PR—remains po…

8112 Background: While immune checkpoint inhibitors (ICIs) have reshaped the therapeutic landscape for extensive-stage small-cell lung cancer (ES-SCLC), they are frequently associated with immune-related adverse events (irAEs) that may lead to treatment disruption. Early prediction of irAEs remains challenging due to their atypical clinical manifestations. This study aimed to identify risk factor…

9579 Background: In resectable high-risk melanoma, neoadjuvant anti–PD-1 aims to exceed the ~40% MPR benchmark; while combos may deepen response, they add tox, complexity, and cost. Recently reported data for prolgolimab+nurulimab (N = 205) showed pCR 38.5%, near-CR 4.4%, motivating evaluation of prolgolimab mono as a simpler potentially non-inferior approach. Methods: MelPRO-0322 (CRISTINA; NCT0…

8533 Background: Response to first-line standard-of-care (SoC) chemo-immunotherapy (IO) for patients with NSCLC without targetable mutations is heterogeneous, highlighting the need for predictive biomarkers. GEMINI (NCT05236114) integrates real-world outcomes, whole exome sequencing (WES), single-cell spatial transcriptomics (SpTx), and AI-pathology to establish a benchmarking resource and patien…

8559 Background: Pembrolizumab plus platinum-based chemotherapy is a standard first-line treatment for previously untreated advanced squamous non-small cell lung cancer (NSCLC) based on the KEYNOTE-407 trial. Ubenimex, an oral CD13/aminopeptidase inhibitor, has immunostimulatory and antitumor activity. We conducted a phase II trial to assess the safety and efficacy of ubenimex in combination with…

8657 Background: Neutropenia is a common dose-limiting chemotherapy toxicity, with its severity and duration impairing therapeutic efficacy. In NSCLC management, chemotherapy regimens with high risk febrile neutropenia (FN) are relatively uncommon. However, real-world data show suboptimal prophylactic granulocyte colony-stimulating factor (G-CSF) use in intermediate risk FN patients with addition…

8622 Background: Sevabertinib, a potent, reversible, oral tyrosine kinase inhibitor, received FDA accelerated approval for pretreated patients with advanced NSCLC harboring HER2 tyrosine kinase domain-activating mutations. Sevabertinib demonstrated significant antitumor activity and manageable safety in patients with HER2 -mutant NSCLC who had previously received treatment (Cohort D) or were trea…