Trial explores potential benefit of adding atezolizumab to usual care for mesothelioma

An ongoing feasibility trial is investigating whether the addition of atezolizumab to usual care can prolong overall survival (OS) in patients with malignant pleural mesothelioma (MPM) [1].

MPM is an orphan disease with few treatment options. Patients with MPM usually receive neoadjuvant chemotherapy followed by surgical resection and adjuvant radiation –a protocol yielding a median OS of 17–25 months. The PD-L1 target has been identified in mesothelioma cells and confers a negative prognosis in MPM. Thus, Prof. Anne Tsao (MD Anderson Cancer Center, TX, USA) and colleagues hypothesised that adding a PD-L1 inhibitor to both neoadjuvant chemotherapy and post-surgical maintenance therapy regimes may prolong OS and designed a phase 1 feasibility study (NCT03228537) to test this hypothesis.

The study includes chemotherapy-naïve patients with resectable mesothelioma. The participants underwent ≥2 cycles of triplet neoadjuvant therapy (i.e. cisplatin, pemetrexed, and atezolizumab), and then surgical resection and optional radiation therapy. Maintenance atezolizumab was then implemented for up to 1 year. The trial’s primary objective was to evaluate the feasibility and safety of this protocol in patients with resectable MPM. Feasibility was defined as having 18/24 (75%) receive ≥1 dose of maintenance therapy; safety was defined as no occurrence of grade 4 or 5 adverse events (AEs).

The feasibility and safety predetermined thresholds were not met. Out of 28 patients recruited, 25 completed ≥2 cycles of triplet neoadjuvant therapy; 18 of these underwent surgical resection. Following surgery, 15 participants took maintenance atezolizumab for 1 year; 3 remain on atezolizumab. The most common treatment-related AEs were fatigue and nausea; 1 patient experienced 3 grade 4 AEs, and 1 reported a grade 5 AE. No new safety signals emerged.

After a median follow-up period of only 10.3 months, median OS has not yet been reached, and median progression-free survival is 18.6 months.

Prof. Tsao concluded that this trial emphasises the challenging nature of neoadjuvant therapy trials in patients with MPM and noted that translational studies are pending.

1. Tsao AS. S1619: A trial of neoadjuvant cisplatin-pemetrexed with atezolizumab in combination and maintenance for resectable pleural mesothelioma. OA 13.01, WCLC 2021, 8–14 September.

 

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Posted on 21 September 202127 March 2024