Dr. Jonathan Goldman stood before the American Society of Clinical Oncology Annual Meeting in May with news that could transform how doctors treat a rare form of lung cancer: a targeted drug called selpercatinib reduced the risk of cancer recurrence by 83% in patients with early-stage RET fusion-positive NSCLC.
The finding matters because even patients who catch their lung cancer early and undergo surgery, radiation, and chemotherapy often face a haunting reality—their cancer comes back. RET fusion-positive lung cancer, while rare (occurring in just 1–2% of non-small cell lung cancer cases), leaves many patients in exactly this situation: treated with curative intent, yet still vulnerable to recurrence. Until now, there was no approved targeted therapy to help prevent that return after standard treatment.
The international phase 3 trial, called LIBRETTO-432, enrolled 151 patients with stage IB–IIIA RET fusion-positive NSCLC who had already received standard treatment. Researchers randomly assigned 75 patients to receive selpercatinib and 76 to receive a placebo, with follow-up continuing for up to three years. The results were stark. After two years, 92% of patients who received selpercatinib with stage II–IIIA disease remained alive without cancer recurrence—what clinicians call event-free survival—compared with just 61% of those given a placebo. Looking at the broader study population across all stages, 94% of selpercatinib recipients remained cancer-free at two years versus 70% in the placebo group.
Selpercatinib works by specifically blocking RET-driven cancer growth. The drug was already approved for patients with advanced or metastatic RET-altered cancers and had shown strong responses in previous studies of later-stage disease. LIBRETTO-432 marked the first randomized study to test whether it could help patients earlier in their disease trajectory, after surgery or other definitive treatment—a critical gap in the treatment landscape. Goldman, a Health Sciences Clinical Professor in the Department of Medicine at the David Geffen School of Medicine at UCLA and co-leader of the study, emphasized the significance in the New England Journal of Medicine, where the findings were also published: "These results have the potential to change clinical practice for patients with early-stage RET-positive lung cancer."
The safety profile remained consistent with earlier studies of the drug. The most common serious side effects involved elevations in liver enzymes, which clinicians typically managed through dose adjustments or temporary treatment pauses—a manageable trade-off for such dramatic risk reduction.
What makes this result particularly meaningful is the narrowness of the population it serves. RET fusion-positive lung cancer is uncommon enough that many oncologists may see only a handful of cases in their careers. Yet for those patients and their families, the finding opens a new door: a way to add protection after surgery, to reduce the specter of recurrence that haunts so many cancer survivors. The research team plans to continue tracking patients to understand whether selpercatinib ultimately improves overall survival and how different patient groups respond to the therapy. For now, the message is clear—early comprehensive biomarker testing, paired with this targeted approach, could keep early-stage RET-positive lung cancer from returning.