Tumour Treating Fields therapy extends OS for mNSCLC after plantinum failure

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Published: 6 Jun 2023
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Dr Ticiana Leal - Emory University, Atlanta, USA

Dr Leal talks to ecancer about data she presented at ASCO 2023 from the phase 3 LUNAR study.

Tumour Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability, delivered by a noninvasive portable device that is FDA approved for glioblastoma and mesothelioma.

TTFields therapy was found to have significantly extended overall survival in patients with metastatic NSCLC following platinum failure without exacerbating systemic toxicities, and with few high-grade device-related AEs.

Dr Leal notes that the efficacy and safety demonstrated in this phase 3 study warrant inclusion of TTFields therapy as part of second line standard of care in metastatic NSCLC.
 

Tumour Treating Fields are electric fields that exert physical forces on electronically charged components of dividing cancer cells. It has an antimitotic effect; the downstream effects of that are immunogenic cell death, triggering a systemic antitumor immune response. In addition, pre-clinical studies have demonstrated that Tumour Treating Fields in combination with taxanes or immune checkpoint inhibitors led to improved efficacy in these models. Previously, a pilot study combining Tumour Treating Fields therapy and pemetrexed demonstrated both the feasibility and safety. So this is the background of the LUNAR study. 

The LUNAR study is a randomised phase III study that was designed to study the safety and efficacy of Tumour Treating Fields therapy plus standard of care, versus standard of care alone in patients with advanced non-small cell lung cancer with prior platinum-based chemotherapy. In our study, 274 patients were randomised 1:1 to either Tumour Treating Fields plus standard of care, standard of care included immune checkpoint inhibitors or docetaxel, versus standard of care. Then patients were followed every six weeks and continued treatment until progression. In our study the baseline patient characteristics and disease characteristics were well balanced between the two groups, and the available PD-L1 status data available did not show any difference. The primary endpoint of the study is overall survival; secondary endpoints include overall survival in the immune checkpoint inhibitor treated subgroup and docetaxel treated subgroups. Other secondary endpoints included progression free survival, overall response rate, overall survival by histologic subgroups, quality of life, and safety. 

The key take-home point of our study is that our study met the primary endpoint of overall survival. What we saw was a statistically significant improvement in overall survival in the ITT population. The median overall survival in the standard of care arm was 9.9 months and then 13.2 months in TTFields plus standard of care. The hazard ratio is 0.74, and the p-value of 0.035. We saw striking improvement in overall survival in the ICI treated subgroup. There we saw a median overall survival of 10.8 months in the control arm versus 18.5 months in the ICI plus TTFields therapy. The curves separated early and maintained separation throughout. Here we saw a hazard ratio of 0.63 and we saw a p-value of 0.03.

In the docetaxel treated subgroup we saw a median overall survival of 8.7 months in the docetaxel treated arm, and then we saw an overall survival of 11.1 months in TTFields plus standard of care. The hazard ratio there of 0.81 and a p-value that was 0.28. 

In addition, we demonstrated the safety of TTFields plus standard of care; overall the treatment was well-tolerated. There were no significant differences in terms of grade 3 or higher adverse events between the two groups. The only notable difference was dermatitis, that was seen more frequently in the TTFields plus standard of care. All grade dermatitis was 43%, however grade three or higher was low at 2%. Dermatitis resolved in 87% of the cases, with a median of about three weeks. 

So overall I think the take-home for this study is that it met its primary endpoint of overall survival. This is potentially a paradigm shifting treatment modality for non-small cell lung cancer, really addressing a population with high unmet needs in the second line and beyond where we’ve only had docetaxel since the approval of docetaxel, and docetaxel plus RAM in 2014.