A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205

Our plain-English summary of A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205, by J. Raskin, V. Surmont, A.P.W.M. Maat, et al (The European Respiratory Journal, 2024).

The study

• Authors: J. Raskin, V. Surmont, A.P.W.M. Maat, M. Yahia, S.A. Burgers, Y. Pretzenbacher, F. De Ryck, R. Cornelissen, H.M. Klomp, A. Oliveira, J. Aerts, P. Baas, S. Marreaud, J.P. Van Meerbeeck, P.E.Y. Van Schil
• Journal: The European Respiratory Journal
• Published: 2024;63(6)
• Type of article: Randomized trial
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown.

Methods: EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3-4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality.

Findings: 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8-81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8-62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5-17.2) months and 27.1 (95% CI 22.6-64.3) months in arm A, and 8.0 (95% CI 7.2-21.9) months and 33.8 (95% CI 23.8-44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high.

Interpretation: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Copyright ©The authors 2024.

In plain English

This randomised phase 2 trial (five hospitals, Belgium, the Netherlands and Egypt, 2016 to 2021) studied treatment order, not asbestos exposure, in early-stage pleural mesothelioma. Of 69 patients, 34 were assigned surgery (extended pleurectomy/decortication) then chemotherapy (arm A), and 35 the reverse (arm B). For the main outcome, each arm was tested against a set threshold, not the other arm. Success at 20 weeks meant both treatments completed on time, being alive without progression, and no lasting severe side effects. Of 64 analysed, 21 of 30 in arm A (70.0%; 80% CI 56.8 to 81.0%) and 17 of 34 in arm B (50.0%; 80% CI 37.8 to 62.2%) succeeded; neither met the threshold. Median overall survival was 27.1 months (95% CI 22.6 to 64.3) in arm A and 33.8 (95% CI 23.8 to 44.6) in arm B, not a statistically significant difference. Of 58 operated patients, 84.5% had at least one surgical complication and one (1.7%) died within 90 days. The authors concluded no preferred sequence could be selected and either approach is feasible, with low mortality but consistent complications.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multicentre, noncomparative, randomised phase 2 trial (EORTC 1205). For the primary end-point, each arm was tested separately for feasibility. Survival was also compared between arms using hazard ratios.
• Who was studied: 69 patients with treatment-naive, early-stage (stage I to III) pleural mesothelioma of any histology, judged borderline resectable and fit for chemotherapy and surgery. They were enrolled between October 2016 and November 2021 at five tertiary-care hospitals in Belgium, the Netherlands and Egypt. 34 were randomised to arm A and 35 to arm B, and 64 (30 in arm A, 34 in arm B) were in the main analysis.
• Exposure: Not an asbestos exposure study. The treatments compared were immediate extended pleurectomy/decortication followed by three cycles of cisplatin plus pemetrexed chemotherapy (arm A), versus the same chemotherapy given first and followed by surgery (arm B). Carboplatin was later allowed in place of cisplatin.
• Main results:
  • Success at 20 weeks (all three criteria met): 21 of 30 patients in arm A (70.0%; 80% CI 56.8 to 81.0%) and 17 of 34 patients in arm B (50.0%; 80% CI 37.8 to 62.2%)
  • Neither arm reached the pre-set feasibility threshold, so neither could be considered successful
  • The difference between arms was mainly due to more patients with progressive disease at week 18 to 22 in arm B (41%) than in arm A (17%). On rechecking 3 months later, all of these patients were still progressing.
  • Overall survival did not differ significantly between arms (HR 1.22, 95% CI 0.64 to 2.34). Median overall survival was 27.1 months (95% CI 22.6 to 64.3) in arm A and 33.8 months (95% CI 23.8 to 44.6) in arm B.
  • Progression-free survival did not differ significantly between arms (HR 1.08, 95% CI 0.61 to 1.92). Median progression-free survival was 10.8 months in arm A and 8.0 months in arm B.
  • Neoadjuvant chemotherapy (arm B) was more often completed in full (91% received all three cycles) than adjuvant chemotherapy (arm A, 71%)
  • Among the 58 patients who had surgery, macroscopic complete resection was achieved in 82.8%
  • 84.5% of operated patients had at least one surgical complication
  • 30-day and 90-day mortality were both 1.7%: one patient in arm A died of a myocardial infarction 2 days after surgery
  • Outcome appeared worse for the eight patients with nonepithelioid histology
• The authors' conclusion: The authors concluded that the trial did not succeed in selecting a preferred sequence of chemotherapy before or after surgery, and that either approach is feasible with low mortality, albeit consistent morbidity. They added that a shared informed decision between surgeon and patient remains essential.
• Limitations the authors state:
  • The composite end-point makes overall treatment success harder to interpret
  • Four arm A patients were excluded for not starting treatment. This unbalanced the arms, left the study underpowered and may have biased the results.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleurectomy/Decortication (P/D), Chemotherapy, Pleural Mesothelioma, Mesothelioma, Histology, Overall Survival, Progression-Free Survival.

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• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma — L. Lang-Lazdunski, A. Bille, et al. (2011)
• Extended Pleurectomy-Decortication-Based Treatment for Advanced Stage Epithelial Mesothelioma Yielding a Median Survival of Nearly Three Years — J.S. Friedberg, C.B. Simone, et al. (2017)
• A Trimodality, Four-Step Treatment including Chemotherapy, Pleurectomy/Decortication and Radiotherapy in Early-Stage Malignant Pleural Mesothelioma: A Single-Institution Retrospective Case Series Study — G. Vicidomini, C.M. Della Corte, et al. (2021)
• Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma — E. Lim, L. Darlison, et al. (2020)

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