medwireNews: Combining tumor treating fields (TTFields) with standard chemotherapy could be a promising option for the first-line treatment of inoperable malignant pleural mesothelioma, say the STELLAR investigators.
They explain in The Lancet Oncology that TTFields are “a non-invasive, regional, antimitotic treatment for solid tumours, that is based on the delivery of low-intensity alternating electric fields to the tumour,” which has demonstrated “promising preclinical results in mesothelioma models.”
This phase II trial enrolled 80 participants who received continuous TTFields to the thorax for at least 18 hours/day at a frequency of 150 kHz alongside up to six cycles of chemotherapy with pemetrexed plus cisplatin or carboplatin, followed by maintenance TTFields for those who did not progress after chemotherapy.
Participants were followed up for a median of 12.5 months, during which time they achieved a median overall survival (OS) of 18.2 months, with 1- and 2-year rates of 62.2% and 41.9%, respectively.
Median progression-free survival (PFS) was 7.6 months, and the objective response rate as per RECIST criteria was 40% (all partial responses) among the 72 evaluable patients. Just over half (56%) of trial participants went on to receive further treatment after disease progression.
In a post-hoc analysis both OS and PFS were found to be longer for the 53 patients with epithelioid histology than for the 27 individuals with non-epithelioid histology, with median times of 21.2 versus 12.1 months and 8.3 versus 6.5 months, respectively.
Giovanni Ceresoli (Cliniche Humanitas Gavazzeni, Bergamo, Italy) and co-authors highlight that “the overall survival results in the STELLAR trial were achieved without an increase in systemic toxicity related to chemotherapy.”
The only adverse event related to TTFields therapy was skin irritation at the site of the medical device, occurring in 66% of patients, but the majority of the cases were of grade 1 or 2, and just 5% of participants discontinued use of TTFields permanently as a result of skin reactions.
The author of an accompanying commentary notes that the trial met its “ambitious” endpoint for TTFields treatment of a median 5.5-month improvement in OS beyond the 12.1 months expected with standard chemotherapy alone, which led to the US FDA approval of TTFields for mesothelioma in May this year.
“However, the question as to whether or not there truly exists a measurable and positive incremental benefit in overall survival conferred by TTFields over historical controls in 2019, remains unanswered,” continues Dean Fennell, from the University of Leicester in the UK.
He highlights some of the limitations of the trial, such as the potential for sampling bias in single-arm studies and the effect of post-trial therapy, and concludes: “In summary, systemic therapy remains the first-line therapy for mesothelioma, but STELLAR presents a promising signal of efficacy that urgently needs reinforcement via the gold-standard of randomised evaluation.”
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Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30532-7
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30642-4