New Hope from ASCO 2026
Each year, the American Society of Clinical Oncology (ASCO) hosts cancer researchers from around the world to share their latest discoveries. At this year’s meeting in Chicago, researchers presented many new findings on ALK-positive lung cancer. The overall message was encouraging: targeted therapies continue to improve outcomes, treatment options are expanding, and researchers are finding new ways to tackle some of the biggest challenges facing people living with ALK-positive lung cancer.
One of the clearest themes to emerge from the conference was that ALK-targeted therapy remains the cornerstone of treatment. Long-term results from the CROWN study continue to demonstrate the remarkable effectiveness of first-line Lorlatinib compared with the older drug Crizotinib. The latest follow-up showed that after more than seven years, over half of the patients who began treatment with Lorlatinib had still not experienced cancer progression or recurrence. We also received an update on the neladalkib (NVL-655) ALKOVE-1 study. The drug continues to show efficacy across lines of therapy and in the CNS. Data in first-line patients is limited in the number of patients. The ongoing phase III trial (ALKAZAR) in first-line patients is much larger and is being compared to alectinib.
Real-world studies from China and other regions confirmed that Lorlatinib performs as well outside of clinical trials. Researchers also presented early results for Deulorlatinib, a next-generation ALK inhibitor designed to provide cancer control similar to Lorlatinib while reducing side effects. Together, these studies reinforce that third-generation ALK inhibitors, particularly Lorlatinib and drugs in the same class, remain the preferred first treatment for advanced and stage IV ALK-positive lung cancer. Crizotinib now serves largely as a historical comparison, while newer ALK inhibitors are demonstrating the ability to provide long-lasting disease control.
Researchers also highlighted how targeted therapy is moving earlier in the course of treatment. Traditionally reserved for metastatic disease, ALK inhibitors are now being explored before surgery for people with early-stage lung cancer. Results from the LORIN trial showed that giving Lorlatinib before lung surgery in stage III disease led to substantial tumor shrinkage, making the surgery easier. Many patients previously considered inoperable became candidates for surgery after Lorlatinib treatment. Additional presentations illustrated how ALK-targeted therapy is now being incorporated across the entire disease journey, including early-stage disease, oligoprogression, and metastatic disease. These findings suggest that targeted therapy is becoming a continuous part of care rather than a treatment reserved only for advanced cancer.
Another important focus at ASCO was the treatment of cancer that has spread to the brain and central nervous system. Historically, these diagnoses carried a poor prognosis, but newer therapies are changing that outlook. A retrospective study of patients with leptomeningeal disease found that third-generation ALK inhibitors improved survival and provided better control of disease affecting the brain and spinal fluid than earlier therapies. The phase III DURABLE clinical trial examined whether radiation to the brain should be given immediately or delayed in patients whose cancer had progressed in the brain. While upfront radiation reduced the likelihood of future brain progression, it did not improve overall survival. The study also found that radiation necrosis occurred in about 30% of participants within twenty-seven months, although most cases were mild to moderate. Taken together, these studies show that brain and central nervous system metastases are becoming more manageable, while emphasizing the importance of choosing ALK inhibitors with strong penetration into the central nervous system and continuing to refine brain-specific treatment strategies.
The conference also reinforced what has become increasingly clear about immunotherapy in ALK-positive lung cancer. A study evaluating chemoimmunotherapy found that tumors driven by ALK mutations continued to derive less consistent benefit from PD-1/L-1 immunotherapy combinations than cancers driven by mutations such as KRAS. These findings support the avoidance of these immunotherapies in ALK.
As patients live longer with ALK-positive lung cancer, researchers are paying increasing attention to the long-term safety of treatment. One study confirmed that elevated cholesterol and triglyceride levels remain common among people taking Lorlatinib and can become clinically significant. Another study found higher rates of both arterial and venous blood clots in patients with ALK- and ROS1-positive lung cancer. These findings reinforce the importance of routine monitoring, including regular lipid testing, timely treatment with cholesterol-lowering medications when appropriate, and the use of anticoagulants due to increased risk of blood clotting.
Finally, researchers offered an early glimpse into a new frontier: preventing drug resistance due to ALK gene mutations before it develops. In the ARCHER study, patients whose cancer remained controlled on ALK-targeted therapy received an investigational peptide vaccine (ALK-Vac) designed to stimulate the immune system against seven common resistance mutations. The study has two primary outcome measures: safety and immune cell activation. Although still experimental, the vaccine proved safe and showed evidence of immune system activation against those mutations.
Overall, this year’s ASCO meeting painted an optimistic picture for the ALK community. Targeted therapies continue to deliver durable, long-term control for many patients; their use is expanding into earlier stages of disease, and advances in brain metastasis treatment, supportive care, and resistance prevention are steadily improving the outlook for people living with ALK-positive lung cancer.
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Author: Ellee Urban
