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Federica Grosso
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P24 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Mesothelioma Clinical and Trials in Progress (ID 138)
- Event: WCLC 2020
- Type: Posters
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 01:00, ePoster Hall
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P24.08 - Radiological Response to TTFields Plus Chemotherapy for Malignant Pleural Mesothelioma from the Phase 2 STELLAR Trial (ID 3545)
00:00 - 01:00 | Presenting Author(s): Federica Grosso
- Abstract
Introduction
Tumor Treating Fields (TTFields) is a regional antimitotic therapy utilizing low intensity alternating electric fields delivered non-invasively to the tumor via a portable device. In the Phase 2 STELLAR trial, TTFields plus first-line chemotherapy led to a promising median overall survival (OS) of 18.2 months in patients with unresectable malignant pleural mesothelioma (MPM) (Ceresoli et al. Lancet Oncol. 2019). This analysis describes the radiological response pattern and responder characteristics from STELLAR.
Methods
The STELLAR trial enrolled 80 patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 and measurable or evaluable disease according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for mesothelioma. Patients were treated with continuous 150 kHz TTFields (≥18h/day) using the Optune Lua® system in combination with pemetrexed and cisplatin or carboplatin at standard dosing. Patients were followed up every 3 weeks, with CT scans every 6 weeks, until disease progression. Radiological assessments were by investigators according to mRECIST. Primary endpoint was OS evaluated in the intent-to-treat (ITT) population. Safety analyses were in all patients who received at least one day of TTFields therapy.
Results
72 patients from STELLAR had at least one follow-up CT scan and were therefore evaluable for response. Partial response (PR) was seen in 40% (29/72) and disease control (PR + stable disease [SD]) in 97% (70/72) of evaluable patients. Out of the 29 responders, 23 (79%) had epithelioid, 4 (14%) had non-epithelioid, and 2 (7%) had unknown histology. The median time between treatment start and PR was 1.9 months (range: 1.4-4.4 months). Based on the radiological data from patients available at each visit, there was a continuous reduction in the total sum of lesion diameters, suggesting no initial/pseudo-progression. Median progression-free survival (PFS) was 9.1 months in the responder relative to 7.6 months in the ITT population. 86% of patients who responded to the combined therapy finally had disease progression with a median duration of response of 5.7 months (range: 1.4-13 months). One patient remains progression-free at 55 months. 28 (97%) responders reported at least 1 adverse event (AE). The only TTFields-related AEs in responders were beneath-array skin reactions (reported by 25 [86%] patients), which were all mild to moderate and manageable. Median TTFields compliance in the first 3 months was 70% (16.8 hours/day) in the responder vs 68% (16.3 hours/day) in the ITT population.
Conclusion
The STELLAR trial showed a meaningfully extended OS when TTFields is added to the current standard of care for first-line treatment of MPM. This benefit was achieved without an increase in the systemic adverse events associated with chemotherapy. Overall response and disease control rates from this analysis are consistent with those previously reported for chemotherapy. TTFields is a safe and effective adjunctive treatment for previously untreated, unresectable MPM.
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P24.09 - Pooled Safety Analysis of Clinical Trials Delivering Tumor Treating Fields (TTFields) to the Upper Torso (ID 3714)
00:00 - 01:00 | Presenting Author(s): Federica Grosso
- Abstract
Introduction
Tumor Treating Fields (TTFields), a non-invasive, loco-regional, antimitotic treatment FDA-approved for glioblastoma (GBM) and malignant pleural mesothelioma (MPM), delivers low intensity alternating electric fields to the tumor via transducer arrays placed directly on the skin. The most common adverse event (AE) related to TTFields treatment from phase III trials in GBM and from a large, post-marketing surveillance study in high grade gliomas was mild to moderate localized dermatitis underneath the arrays. Delivery of TTFields to the upper torso has been investigated in non-small-cell lung cancer (NSCLC) [EF-15, NCT00749346] and malignant pleural mesothelioma (MPM) [STELLAR, NCT02397928]. A pooled analysis of AE data from these studies was conducted to confirm the safety of TTFields when applied to the thorax.
Methods
EF-15 was a phase I/II trial of TTFields plus pemetrexed for pretreated, advanced NSCLC. STELLAR was a phase II trial of TTFields plus pemetrexed and cisplatin or carboplatin for previously untreated, unresectable MPM. Both studies enrolled adult patients (≥18 years of age) with a life expectancy of ≥12 weeks and pathologically confirmed, measurable or evaluable disease. Patients were treated with 150 kHz TTFields to the thorax using the NovoTTF-100L system for 12-18 hours/day plus standard of care systemic chemotherapy. Patients were followed up every 3 weeks until disease progression. Adverse event terms and grading were according to Common Terminology Criteria for Adverse Events (CTCAE version 4.0). The incidence, severity, and relatedness of the pooled AEs to TTFields therapy were evaluated.
Results
The analysis included 121 patients treated with TTFields to the upper torso from EF-15 (n=41) and STELLAR (n=80). Patients were aged 27-78 years. The median age was 63 (range: 44-78) and 67 (range: 27-78) years in EF-15 and STELLAR, respectively. All patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, except for 7 patients in EF-15 who had an ECOG PS of 2. The most commonly reported AEs were dermatologic, gastrointestinal (GI), and general disorders. 59% of patients had dermatological AEs (Grade 1-2 [53%] and Grade 3 [4%] dermatitis, and Grade 1-2 pruritus [11%]). The only common TTFields-related AE was beneath-array dermatitis. Grade 1-2 GI AEs were reported by 35% of patients (nausea [17%], vomiting [6%], constipation [10%], and diarrhea [6%]). 27% of patients reported Grade 1-2 general disorders (fatigue [16%] and asthenia [11%]). Grade 1-2 (12%) and Grade 3-4 (5%) dyspnea were considered related to standard chemotherapy or underlying disease. Grade 1-2 cardiovascular AEs were reported by 7% of patients. One case of severe arrhythmia (atrial flutter) was reported and was assessed as unrelated to TTFields.
Conclusion
This pooled analysis revealed no new safety signals related to treatment of solid tumors with 150 kHz TTFields applied to the upper torso. Treatment with TTFields was not associated with serious AEs or device-related pulmonary, cardiac, hematological or gastrointestinal toxicities. Expected dermatological AEs beneath the arrays were mostly mild to moderate and manageable. TTFields delivered to the thorax was safe and well-tolerated.
