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TTFields in NSCLC
The Potential of TTFields Therapy in the Treatment of Advanced NSCLC: Expert Discussion of the Phase III LUNAR Trial

Released: July 12, 2023

Ticiana Leal
Ticiana Leal, MD
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Key Takeaways
  • The second-line setting for advanced NSCLC without an actionable mutation is an area of unmet need.
  • Tumor treating fields (TTFields) therapy involves a novel device delivering electric fields that disrupt dividing cancer cells and lead to an antitumor immune response.
  • The phase III LUNAR trial demonstrated an overall survival benefit for adding TTFields therapy to immune checkpoint inhibition or docetaxel in the setting of recurrent advanced NSCLC.
  • Dermatitis is a common treatable and preventable adverse event with the TTFields device in patients with advanced NSCLC.

Patients with advanced non-small-cell lung cancer (NSCLC) without an actionable mutation have limited treatment options following progression of their disease on first-line chemoimmunotherapy. The current approach includes mainly docetaxel with or without ramucirumab, and immune checkpoint inhibitor monotherapy for patients who did not receive it in the frontline. There is a pressing need for new, effective, and well-tolerated treatment strategies for patients with advanced NSCLC in the second line and beyond.

What Are Tumor Treating Fields?

Tumor treating fields (TTFields) are alternating electric fields that disrupt cancer cell division, leading to immunogenic cell death and triggering of a systemic antitumor effect. Prior preclinical studies showed the efficacy of TTFields in combination with taxanes or immune check point inhibitors, and a subsequent single-arm phase I/II pilot study demonstrated the clinical feasibility of TTFields combined with pemetrexed in patients with recurrent advanced NSCLC. TTFields are currently approved by the FDA for use in glioblastoma and malignant pleural mesothelioma. 

In lung cancer, TTFields therapy is delivered locoregionally to the chest by a wearable medical device and 2 pairs of arrays. The manufacturer generates a recommended personalized array layout based on disease burden and torso size to maximize field intensity at the tumor location. The device is delivered to the patient’s home with 24/7 phone support by a device technician, and it is recommended for continuous use for approximately 18 hours per day. Throughout the course of TTFields therapy, the treating oncologist continues to provide all standard systemic therapy and patient care.

LUNAR: TTFields Therapy Plus Immune Checkpoint Inhibition or Docetaxel in Recurrent Advanced NSCLC

LUNAR was a pivotal, global, randomized phase III study designed to evaluate the safety and efficacy of TTFields therapy in combination with standard of care (SoC) therapy, either immune checkpoint inhibition or docetaxel, compared with SoC alone in patients with advanced NSCLC who progressed on or after platinum-based chemotherapy (N = 276). 

The LUNAR study met is primary endpoint of improved overall survival (OS) in the intention-to-treat population with a median OS of 13.2 months in the TTFields plus SoC arm compared with 9.9 months in the SoC arm (HR: 0.74; P = .035). In the subgroup of patients receiving an immune checkpoint inhibitor, there was a striking OS benefit with a median OS of 18.5 months in the TTFields plus SoC arm vs 10.8 months in the SoC arm (HR: 0.63; P = .03). In the docetaxel subgroup, the median OS was 11.1 months in the TTFields plus SoC arm vs 8.7 months in the SoC arm (HR: 0.81; P = .28). These clinical results are in line with prior preclinical studies demonstrating that TTFields combined with immune checkpoint inhibitors leads to immunogenic cell death and triggers a systemic antitumor immune response.

Safety of TTFields Therapy in Patients With Advanced NSCLC

Overall, TTFields therapy in combination with SoC was well-tolerated. The incidence of grade ≥3 adverse events (AEs) was comparable between arms. There were no grade 4 AEs or deaths attributable to TTFields therapy, nor were there any notable differences in health-related quality of life when TTFields was added to SoC.

The only notable difference in AE incidence between the arms was dermatitis—43% with TTFields plus SoC vs 2% with SoC—and most cases were grade 1-2. However, the rate of grade ≥3 dermatitis with TTFields plus SoC was low at 2%. Of note, dermatitis resolved in 87% of cases, with a median duration of 3 weeks. To mitigate the development of dermatitis prior to array application, the skin should be cleaned and well-shaven. The transducer arrays should be replaced every 3-4 days, allowing several hours between array removal and replacement, along with repositioning them by approximately 2 cm to an alternative layout. If there is evidence of dermatitis, topical treatments such as corticosteroids or antibiotics can be prescribed. If the dermatitis persists, a 2- to 7-day treatment interruption can be considered.

Conclusions

In summary, the LUNAR study led to a statistically significant and clinically meaningful improvement in OS, addressing a population of patients with advanced NSCLC in the second line and beyond with high unmet need. Additional studies evaluating TTFields therapy with current SoC for first-line metastatic and locally advanced NSCLC are underway.

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