
Welcome to The Five Under 5, your concise and impactful weekly video roundup designed especially for busy oncologists eager to stay updated without sifting through endless articles. Each video offers expert insights into the most vital developments in oncology, covering breaking news, regulatory approvals, practice-changing clinical data, and emerging therapies unveiled at major medical conferences. The beauty of these short briefings lies in their ability to distill complex, cutting-edge oncology research into digestible knowledge you can absorb on the go—whether during a hectic clinic day or in between patient consultations.
Let's dive into what you might have missed this week, starting with groundbreaking advances in the management of myelodysplastic syndrome (MDS). Dr. Amer Zeidan from Yale Cancer Center shared updates on several promising clinical trials exploring novel therapeutic agents. Notably, the PD-L1 inhibitor durvalumab (Imfinzi), despite initial hopes, did not demonstrate significant clinical benefit in a phase 1 trial. However, the spotlight shifts to sabatolimab (MBG453), a TIM-3 inhibitor, which showed early signs of efficacy in the STIMULUS-MDS1 trial. Although the subsequent phase 3 STIMULUS-MDS2 trial revealed only a numerical, but not statistically significant, overall survival advantage when combined with azacitidine (Vidaza), ongoing studies remain optimistic. The phase 3 VERONA trial evaluating azacitidine plus venetoclax (Venclexta), and the ELEMENT-MDS trial assessing luspatercept-aamt (Reblozyl), are eagerly anticipated. What’s particularly fascinating is the expanding landscape of early-phase research into agents like tebipivat (AG-946), AK117, and bexmarilimab, marking a vibrant era of innovation in MDS treatment. A quirky note: MDS is sometimes called a “bone marrow failure syndrome,” but with therapies evolving, its reputation as a grim diagnosis is steadily being rewritten.
In the realm of lung cancer, Dr. Elaine Shum of NYU Langone’s Perlmutter Cancer Center sheds light on a pivotal evolution in treating EGFR-mutated non–small cell lung cancer (NSCLC). Osimertinib (Tagrisso) monotherapy has long been regarded as the frontline standard, prized for its efficacy and ability to penetrate the brain, a common site of metastasis. Yet, new strategies are emerging to counteract resistance and improve the durability of response. The phase 3 FLAURA2 trial demonstrated that adding platinum-based chemotherapy to osimertinib significantly improved progression-free survival. Adding to this, the MARIPOSA trial propelled the combination of amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze) into the limelight, securing FDA approval in August 2024. This represents a paradigm shift favoring combination regimens for selected patients, especially those at high risk of early disease progression. Interestingly, EGFR mutations were first identified back in 2004 as drivers in NSCLC, underscoring how far targeted therapy has come—from discovery to sophisticated, personalized combinations within two decades.
Hepatocellular carcinoma (HCC) treatment also reached a milestone, with Dr. James J. Harding from Memorial Sloan Kettering Cancer Center discussing the impact of dual checkpoint blockade. The CheckMate 9DW trial led to the FDA’s approval in April 2025 of nivolumab (Opdivo) plus ipilimumab (Yervoy) as first-line therapy for unresectable or metastatic HCC. This combination demonstrated a significant overall survival benefit compared to standard therapies sorafenib and lenvatinib, with Kaplan-Meier survival curves diverging at 12 months and nearly half of patients still alive at two and three years. While progression-free survival (PFS) did not show a statistically significant difference, the dual immunotherapy boasted a higher objective response rate—36.1% versus 13.2% in the control arm—highlighting more complete and partial responses. These durable results reaffirm the value of CTLA-4-based combinations and position them firmly as frontline standards for advanced HCC. On an intriguing tangent: the liver’s immune environment is uniquely immunosuppressive, making these robust immunotherapy responses all the more remarkable given the organ's natural resistance to immune attack.
Finally, Dr. Van K. Morris of the MD Anderson Cancer Center highlights the promising advances in microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) colorectal cancer (CRC). The phase 3 CheckMate 8HW trial supported the April 2025 FDA approval of nivolumab plus ipilimumab for untreated patients with unresectable or metastatic disease. Compared to nivolumab monotherapy, the combination produced a notable progression-free survival benefit and improved objective response rates, with two-year PFS rates of 71% versus 56% and ORRs of 71% versus 58%, respectively. Interestingly, benefit was consistent across different tumor locations, metastatic sites, and even in patients with BRAF V600E mutations, a notoriously aggressive subtype. These findings strongly back dual checkpoint blockade as a preferred frontline option. Fun fact: MSI-H tumors typically have a high mutational load, which paradoxically makes them more visible to the immune system—explaining why immunotherapy can be particularly effective for this subgroup.
In summa, this week’s oncology updates reflect remarkable progress across several challenging cancer types. From novel agents in MDS to nuanced combination strategies in lung cancer, and from dual immunotherapy breakthroughs in liver and colorectal cancers, these developments underscore an exciting era where precision medicine, immunotherapy, and combinatorial regimens are reshaping clinical practice. The Five Under 5 continues to deliver these vital insights quickly and efficiently, empowering oncologists to stay at the forefront of transformative science without missing a beat.
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