At the 2023 ASCO Annual Meeting, Ticiana Leal, MD, Winship Cancer Institute at Emory University in Atlanta, Georgia presents on the results from the phase 3 LUNAR trial, evaluating the use of tumor treating fields. This study met its primary end point, improving the overall survival of patients with non-small cell lung cancer who were treated with tumor treating fields plus standard of care.

Dr Leal stated, there was “a significant improvement in overall survival that was statistically and clinically meaningful with a 3-month improvement in median overall survival versus standard of care for patients who received tumor treating fields therapy plus standard of care with no added systemic toxicities.”

Transcript:

My name is Dr Ticiana Leal. I'm an associate professor and director of the thoracic oncology program at the Winship Cancer Institute of Emory University at Atlanta, Georgia. At this year's 2023 ASCO Annual Meeting, on behalf of my co-investigators, I had the honor to present the abstract "Tumor treating fields therapy with standard of care in metastatic non-small cell lung cancer after platinum-based therapies: The randomized, phase 3 LUNAR study," for patients with advanced non-small cell lung cancer.

In the frontline, patients receive the standard chemotherapy with platinum-based chemotherapy with immune checkpoint inhibitors for patients that lack a driver mutation. However, most patients develop disease progression and current approaches in the second-line and beyond remain limited and include mainly docetaxel with or without ramucirumab or immune checkpoint inhibitors for eligible patients. There remains a need for new, well-tolerated and effective second-line therapies.

Tumor treating fields are electric fields that exert physical forces on charged intracellular components, and they've been shown to have an anti-mitotic effect. Downstream effects include immunogenic cell death, which triggers a systemic anti-tumor immune response. In preclinical models, tumor treating fields have shown a decrease in tumor volume when you add tumor treating fields, plus PD-1/PD-L1 inhibitors versus each therapy alone or control. In addition, the combination of tumor treating fields with chemotherapy such as taxanes, or immune checkpoint inhibitors, also led to decreased viability of tumor cells and non-small cell lung cancer cell lines.

The tumor treating fields therapy is delivered as a non-invasive treatment modality. It is delivered locoregionally to the chest by a wearable medical device and 2 pairs of arrays. The device itself is delivered to the patient's home by a device support technician once this is prescribed by the clinician. The recommendation is for continuous use for 18 hours a day. Prior pilot study demonstrated that the use of tumor treatment fields plus pemetrexed chemotherapy was safe and feasible in patients with advanced non-small cell lung cancer who had been previously treated with platinum-based chemotherapy. This was the rationale for the development and design of the LUNAR phase 3 study.

The LUNAR study was a global pivotal study evaluating the safety and efficacy of tumor treating fields therapy with standard of care compared to standard of care alone in patients with metastatic non-small cell lung cancer who had progression on or after platinum-based chemotherapy. In this study, patients with ECOG performance status of 0 to 2 were randomized 1-to-1 to tumor treating fields therapy and standard of care, which included investigator's choice of immune checkpoint inhibitors or docetaxel versus standard of care alone. Patients were then followed every 6 weeks and continued on therapy until disease progression. With regards to patient baseline care characteristics, there were no significant imbalances between the 2 groups.

This study met its primary end point of overall survival. The primary end point led to improved overall survival in the patient population that received tumor treating fields plus standard of care with a median overall survival of 13.2 months versus 9.9 months in the standard of care with a hazard ratio of 0.74.

Secondary end points included overall survival in the immune checkpoint inhibitor (ICI) and the docetaxel treated subgroups. We saw in the ICI-treated patients a particularly meaningful improvement in overall survival with a median overall survival of 18.5 months in tumor treating fields plus ICI versus 10.8 months in the ICI alone group. The hazard ratio is 0.63. In the patients treated with docetaxel, the median overall survival was 11.1 months in the tumor treating fields plus docetaxel versus 8.7 months in the docetaxel alone arm with a hazard ratio of 0.81.

With regards to progression-free survival, the progression-free survival was similar between the 2 groups. With regards to overall response rate, the overall response rate was 20% in tumor treating fields plus standard of care versus 17% in the standard of care alone arm. Of note, there were 5 complete responses in patients receiving ICI, 4 with tumor treating fields therapy and 1 with immune checkpoint inhibitor alone, and we're still analyzing patterns of progression infield versus outfield.

With regards to safety, the majority of patients had 1 or greater adverse event. There were comparable incidents of grade 3 or higher adverse events between subgroups. There were no differences with regards to immune-related adverse events including pneumonitis. Importantly, the most significant difference in terms of side effects that we saw was dermatitis, which was seen in 43% in patients with tumor treating fields plus standard of care versus 2% in the standard of care alone arm. However, the majority of these were grade 1 and 2 in nature, and the majority resolved with a median duration of 3 weeks. There were no grade 4 toxicities, and importantly, no deaths attributable to tumor treating fields therapy.

In summary, in this pivotal phase 3 study called the LUNAR study, we saw a significant improvement in overall survival that was statistically and clinically meaningful with a 3-month improvement in median overall survival versus standard of care for patients who received tumor treating fields therapy plus standard of care with no added systemic toxicities. Additional studies are actually evaluating tumor treating fields now in the frontline setting with immune checkpoint inhibitors, as well as in patients with locally advanced non-small cell lung cancer.

Source:

Leal T, Kotecha R, Ramlau R, et al. Tumor treating fields (TTFields) therapy with standard of care (SOC) in metastatic non-small cell lung cancer (mNSCLC) following platinum failure: Randomized phase 3 LUNAR study. Presented at the 2023 ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. LBA9005