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What’s New in Oncology? – Key Updates from Recent Research
Welcome to the latest edition of What’s New in Oncology?, your go-to source for the most current insights in cancer research. This week, we’re diving into groundbreaking studies from the Journal of Clinical Oncology and other leading publications, covering metastatic prostate cancer, breast cancer, lung metastasis, and neuroblastoma. Here’s a detailed breakdown of the latest findings that are shaping the future of oncology.
KEYNOTE-921 Trial: Immunotherapy in Metastatic Castration-Resistant Prostate Cancer (MCRPC)
A new article from the Journal of Clinical Oncology explores the KEYNOTE-921 trial, a randomized, double-blind, Phase III study led by a global team including Daniel Petrylak and Karim Fizazi. This trial tested Pembrolizumab plus Docetaxel against Docetaxel alone in patients with metastatic castration-resistant prostate cancer (MCRPC) who had previously tried androgen receptor pathway inhibitors like abiraterone. Over 1,000 men across 224 centers were enrolled and tracked for years to assess whether adding an immune checkpoint inhibitor to chemotherapy could improve outcomes.
The results, however, were not the “knockout punch” hoped for. Radiographic progression-free survival (rPFS) was 8.6 months with the combination versus 8.3 months with Docetaxel alone, while overall survival (OS) was 19.6 months versus 19 months—a near tie. Subgroup analyses, including PDL1 status, showed no significant differences. On the safety front, 94% of patients experienced side effects like fatigue and diarrhea in both arms, but pneumonitis occurred more frequently with Pembrolizumab (7% vs. 3%). Researchers suggest that prostate cancer’s immunosuppressive nature may be limiting immunotherapy’s effectiveness. While the trial didn’t pinpoint specific beneficiaries (e.g., those with high tumor mutation burdens), the 19-month OS with Docetaxel alone provides a solid benchmark for future trials. The takeaway? Don’t overhype immunotherapy here without stronger evidence—MCRPC remains a tough challenge to tackle.
For the full dive, check the JCO link: https://ascopubs.org/doi/10.1200/JCO-24-01283
CDK4 Selective Inhibition: A New Approach to Breast Cancer
Next, an article from Cancer Cell introduces Atermaciclib (PF-07060060), a next-generation CDK4-selective inhibitor developed by Pfizer, targeting hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. Led by Cynthia L. Palmer and Lars Anders, the team conducted preclinical tests across cell lines, animal models, and beagle dogs to evaluate its efficacy and safety compared to dual CDK4/6 inhibitors like Palbociclib.
The key insight? Atermaciclib’s 30-fold selectivity for CDK4 over CDK6 reduces neutropenia—a major side effect of dual inhibitors—while enhancing tumor control in HR+ breast cancer models. Since HR+ breast cancer cells rely more on CDK4 than CDK6 for growth, and CDK6 supports bone marrow function, sparing CDK6 minimizes collateral damage. Dog studies showed a 31-fold higher dose tolerance before neutrophil drops matched Palbociclib levels, allowing deeper CDK4 inhibition and superior tumor suppression in mice and spheroids. The team also explored combinations with endocrine therapy or CDK2 inhibitors to address resistance from Cyclin E1 or estrogen signaling—a smart move to broaden its impact.
The catch? CDK6 expression can rise in resistant cells, and while Phase I trials hint at promise, full clinical proof is lacking. This selectivity could be a game-changer, dodging neutropenia while hitting tumors harder, but real-world patient data is needed. The firm conclusion: prioritizing CDK4 coverage over broader CDK6 inhibition offers better efficacy, making neutropenia a trade-off worth avoiding. This could reshape HR+ breast cancer treatment with safer, stronger options.
For more details, see the Cancer Cell link: https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00058-3
Brd7 Loss: An Epigenetic Biomarker for Breast Cancer Metastatic Relapse
An MD Anderson study featured in Nature Communications uncovers how losing Brd7, a component of the PBAF chromatin remodeling complex, triggers breast cancer metastatic relapse in the lungs. Led by Ganta Mondal, PhD, and Jason Hughes, MD, PhD, alongside Filippo Johncotti and others, the team used in vivo screens, mouse models, flow cytometry, and single-cell data to identify Brd7 as a gatekeeper of dormancy.
When Brd7 is lost, it rewires the epigenome, amplifies oncogenic signals, and creates an immunosuppressive niche in the lungs. This niche reduces MHC-I expression, increases pro-metastatic cytokines, and recruits tumor-friendly neutrophils and exhausted T-cells (CD8+ and CD4+ stress response types), waking dormant cells to drive metastasis. The team demonstrated that depleting neutrophils, blocking their NETs with sivelestat, or using anti-CTLA-4 checkpoint inhibitors can halt this outgrowth—a clever strategy with potential.
The data is light on when or how Brd7 loss occurs in humans, though mouse lungs suggest a lung-specific trigger. This leap linking epigenetics to immune evasion is significant, but clinical translation requires more human evidence. The firm takeaway: targeting this immunosuppressive environment—via neutrophils or T-cell exhaustion—could be a game-changer for preventing relapse, offering new therapeutic possibilities.
Dive deeper with the Nature Communications link: https://www.nature.com/articles/s41467-025-56347-2
Neuroblastoma Mutations: Genetic Insights from the Children’s Oncology Group
Finally, a Journal of Clinical Oncology article from the Children’s Oncology Group examines the frequency and clinical significance of clonal and subclonal driver mutations in high-risk neuroblastoma at diagnosis. Led by Esther R. Berko, MD, PhD, and Yael P. Mossé, MD, from the Children’s Hospital of Philadelphia, the team used ultra-deep sequencing on 242 pre-therapy tumors from the ANBL0532 trial, focusing on ALK and RAS/MAPK pathways.
The findings? ALK aberrations were detected in 24.8% of tumors (21.5% mutations, 3.3% amplifications), with five-year overall survival dropping to 37.7% versus 66.3% in ALK wild-types. RAS/MAPK mutations appeared in 7.9% of cases, slashing survival to 19.1% at a ≥5% variant allele frequency (VAF). Even subclonal mutations at ≥5% VAF, especially with MYCN amplification, worsened outcomes, signaling the need for early detection. High-risk neuroblastoma’s 50% survival rate despite aggressive therapy, and frequent relapse with these mutations, underscores the study’s impact.
The challenge? Ultra-deep sequencing reveals more mutations, but small sample sizes (e.g., stage three cases) leave some questions unanswered. This could redraw risk lines, pushing ALK/RAS-mutated cases into an ultra-high-risk category, potentially warranting upfront therapies like Lorlatinib. The firm conclusion: mutations at ≥5% VAF are red flags for worse prognosis, demanding tailored treatment from day one.
Explore the full study at the JCO link: https://ascopubs.org/doi/10.1200/JCO-24-02407
Final Thoughts
This episode of What’s New in Oncology? offers a reality check on MCRPC, innovative hope for breast cancer, a wake-up call on metastasis, and a game-changer for neuroblastoma. These studies highlight the ongoing hunt for effective cancer treatments and the importance of precision medicine. Thank you for tuning in—more episodes drop each week, so stay connected for the latest updates!
Outbound Links:
- JCO – KEYNOTE-921 https://ascopubs.org/doi/10.1200/JCO-24-01283
- Cancer Cell – CDK4 Inhibition https://www.cell.com/cancer-cell/fulltext/S1535-6108(25)00058-3
- Nature Communications – Brd7 Loss https://www.nature.com/articles/s41467-025-56347-2
- JCO – Neuroblastoma Mutations https://ascopubs.org/doi/10.1200/JCO-24-02407
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