Gendered Experience of Mesothelioma Study

EVOLVING STANDARDS OF CARE

TTFields in Unresectable MPM: STELLAR Results in Practice

By Giovanni Luca Ceresoli, MD the only adverse event related to the device was skin irritation underneath Tumor-treating fi elds (TTFields) are a the transducer arrays. Grade 1-2 dernoninvasive, regional treatment based matologic adverse events (dAEs) were on the delivery of low-intensity alternatobserved in 66% of patients; only 5% ing electric fi elds by transducer arrays had grade 3 skin toxicity, leading to applied to the patient’s skin surroundtemporary or permanent interruption ing the tumor. 1 TTFields extend survival of the treatment. In the majority of in glioblastoma and are U.S. Food and cases, dAEs were managed with topical Drug Administration (FDA) approved corticosteroids, short treatment breaks, for newly diagnosed and recurrent and a regular shift ing of 1-2 cm at each glioblastoma. Th e STELLAR trial 2 was array change. a prospective, phase II, single-arm As with any single-arm phase II pilot study in which patients study, the STELLAR trial has with unresectable maligobvious limitations, sugnant pleural mesogesting that further data thelioma (MPM) are needed before there received treatment can be widespread with TTFields, delivimplementation of ered continuously by this therapeutic stratthe NovoTTF-100L egy in clinical practice. system at a frequency However, sample size of 150 kHz, for a planned daily duration of at least 18 Dr. Giovanni Luca Ceresoli was relatively large for a trial in this rare malighours/day. Chemotherapy nancy, and patient baseline with intravenous pemetrexed and platicharacteristics, including ECOG pernum (cisplatin or carboplatin, accordformance status, were in line with other ing to the investigator’s choice) was recent MPM studies, such as the MAPS 4 administered concomitantly at standard and LUME-Meso 5 trials. Of note, 26% doses, for up to 6 cycles. Patients whose of patients on the STELLAR trial had disease did not progress aft er the coma non-epithelioid tumor, a recognized bined TTFields/chemotherapy regimen negative prognostic factor in MPM. Th e received maintenance TTFields alone primary outcome measure of the study until unacceptable toxicity, progreswas OS, which, as of 2020, should be sion, or patient refusal intervened. Th e the standard endpoint for trials in primary endpoint of the trial was OS, advanced MPM, as stated by a recent and the secondary endpoints were PFS, consensus report. 6 Endpoints assessed overall response rate (ORR) according to radiographically, such as ORR and PFS, modifi ed RECIST criteria 3 per investigaare challenging in this disease, especially tor’s assessment, 1- and 2-year survival, if a central radiographic review is not and safety. planned. Of note, OS of patients on the

Eighty patients were enrolled and STELLAR trial was likely not biased by included in the fi nal analysis. Th e study post-study treatments (Fig. 2). results showed that TTFields applied to Based on the results of the STELLAR the thorax in combination with pemetrial, the FDA has approved the use of trexed and platinum were an active TTFields with pemetrexed/platinum for and safe option in the frontline treatthe treatment of unresectable locally ment of unresectable MPM. Median advanced or metastatic MPM, under the OS was 18.2 months, with 1-year and Humanitarian Device Exemption path2-year OS of 62% and 42%, respectively way. 7 Th is is the fi rst FDA approval to (Fig.1). Patients with epithelioid subbe granted for mesothelioma since 2004. type had a median OS of 21.2 months versus 12.1 months for those with nonAreas of Improvement epithelioid tumors. Overall median TTFields act mainly by disrupting the PFS was 7.6 months: 8.3 months in mitotic spindle, but the molecular deterpatients with epithelioid tumors versus minants that aff ect tumor sensitivity are 6.5 months in patients with non-epicurrently unexplored. The treatment thelioid tumors. A partial response was continues to be studied both preclinically observed in 29 (40%) of 72 evaluable and clinically in MPM as well as in other patients. No increase in systemic toxsolid tumors, such as lung, pancreatic, icity was reported with the addition of ovarian, liver, and gastric cancers. Th e TTFields to standard chemotherapy; recent availability of an animal model

Fig. 1. STELLAR Trial: Overall Survival

Median OS was longer in patients with epithelioid histology (21.2 months) than in those with non-epitheliod histology (12.1 months). Ceresoli et al, Lancet Oncol 2019

Fig. 2. STELLAR Trial: Post-Study Treatments

Patients could have more than one subsequent anticancer therapy. Data were not available in 2 patients. Ceresoli et al, Lancet Oncol 2019

Fig. 3. Improving Patient Compliance: Skin Care

Each set of arrays should be changed at least every 3-4 days. More frequent array changes may be required in some patients (e.g., during warmer weather or after intense physical activity.)

Careful removal of arrays (taking approximately 60 seconds to remove each array). Excessive force should be avoided. Use mineral (baby) oil on the edge of the arrays during removal.

Shift the arrays of 1-2 cm from the previous position at each change. The skin must be completely dry before applying a new set of arrays.

If there are signs of dermatitis, early treatment with a highpotency topical corticosteroid is recommended (e.g., clobetasol 0.05%, betamethasone 0.05%). When the epidermal barrier is compromised (erosions) or when there are signs of infection, topical antibiotics are recommended.

Lacouture et al, Semin Oncol 2014

using this technology 8 could contribute to the identifi cation of biomarkers predictive of benefi t. dAEs were the only toxicities directly related to TTFields in the STELLAR trial. Although generally low-grade, easily manageable events, dAEs require the physician’s attention to ensure they do not lead to treatment breaks (Fig. 3). Th ey can occur as a result of a number of diff erent stimuli, including repetitive mechanical trauma (as in the application and removal of the arrays and in shaving) and infl ammation (from the adhesive patch or from the hydrogel covering the ceramic discs). 9 A recent metaanalysis 10 evaluated the adverse events observed in 192 patients enrolled in four pilot clinical studies addressing diff erent cancers, where TTFields in combination with chemotherapy were delivered to the torso. Consistent with STELLAR, dAEs occurred in 58% of cases; low-grade dermatitis was reported in 53% and high-grade in 6%. Low-grade pruritus was reported in 9%. Th ere were no other signifi cant TTFields–related AEs.

Quality-of-life (QoL) data assessment was not planned in the STELLAR trial. A secondary analysis of the phase III EF-14 trial in newly diagnosed glioblastoma showed no adverse effect on QoL for the addition of TTFields to standard chemotherapy, except for more itchy skin, an expected consequence from the transducer arrays. 11 Similarly, the use of the device is not expected to lead continued on page 11