This document summarizes the current management of mesothelioma. It is a rare cancer associated with asbestos exposure. Treatment involves a multidisciplinary approach, with systemic chemotherapy as the mainstay. Around 20% of patients may be candidates for surgical resection combined with radiation and chemotherapy, though the evidence for an overall survival benefit is limited. Immunotherapy with nivolumab and ipilimumab shows benefit compared to chemotherapy for non-epithelioid histologies. Ongoing trials are further evaluating the roles of surgery, radiation therapy, and novel systemic therapies in treatment.

1. Dr. Sayan Das
Medica Superspecialty Hospital, Kolkata
Mesothelioma - An update in
Management

2. Introduction
• Rare cancer in the world - even rarer in India; < 10-12 cases annually in
tertiary cancer centres
• Occurs mostly at an elderly age – ( median age at diagnosis > 60-70 years ) in
people with exposure to asbestos , although occurs decades (20-40yrs) after
exposure
• Other risk factors - previously irradiated patients with mantle fields, genetic
mutations – BAP-1 , smoking
• Median OS is 1 year and 5 y-OS is about 10%

3. Staging Mesothelioma
• Goal of staging: Identify pts
who may benefit from surgery
• Assess baseline ds burden
and organ function before
therapy
• Stage and histology are the
strongest prognostic factors

4. Treatment Algorithm
Popat et al. Ann Oncol 2022

5. Management of Mesothelioma
• A multidisciplinary team approach to assess extent of ds, pt’s general condition/
comorbidities/ cardiopulmonary function/ pt preference
• Around 20% of pts may be candidates for a macroscopic complete resection
• For pts with surgically resectable disease
limited to one hemithorax without any medical
contraindication -> combined-modality
approach
• For others -> systemic therapy and/or
symptom-directed t/t

6. Systemic Therapy
• Checkmate 743: Phase III RCT (n=605) in advanced, t/t-naïve mesothelioma
• Pts were assigned to nivolumab plus ipilimumab for up to 2 yrs, or platinum
plus pemetrexed for up to six cycles
• At a median F/U of 30 months, the median OS in the nivo/ipi group was 18
months, vs 14 months (HR 0.74). 3yr OS - 23% vs 15%
• In subgroup analysis, benefit was seen in nonepithelioid histologies (18 versus
9 months (HR 0.46), but not for epithelioid histology (19 vs 17 months)
Baas et al. Lancet 2021; 397:375.
Peters S, Scherpereel A, Cornelissen R, et al. Ann Oncol 2022; 33:488.

7. Choice of Systemic therapy
• In epithelioid histology: Pemetrexed plus platinum (4-6#) or Nivo/Ipi
• In non-epithelioid histology: Nivo/Ipi preferred
• Maintenance Pemetrexed - limited data
• Addition of Bevacizumab to chemo - MAPS study
Zalcman et al. Lancet 2016; 387:1405.

8. Second line therapy
• For pts initially treated with Immunotherapy -> start chemotherapy
• For pts initially treated with chemo:
Progression > 6 mo: re-challenge with Pem/ Platinum doublet
Progression ≤ 6mo: options include SA Nivo or Gem or Vinorelbine or
Anthracyclines
• PROMISE trial: Pembro vs Gem or Vino - no diff in OS/PFS
• CONFIRM trial: Nivo vs placebo - improved PFS/OS
Popat et al. Ann Oncol 2019; 30S: ESMO #LBA91_PR.
Fennell et al. Lancet Oncol 2021; 22:1530

9. Combined Modality Approach
• Includes a definitive surgical procedure (extrapleural pneumonectomy or
pleurectomy/decortication), combined with RT and chemotherapy
• No randomised evidence showing OS benefit with this approach
• Contemporary case series has shown relatively prolonged survival compared to
chemotherapy alone
• Many centres offer surgery-based t/t to pts with epithelial subtype only

10. MARS
• Initially designed as RCT ->
changed to feasibility study
• 112 pts were treated with
induction chemo -> 50 pts were
randomly assigned to EPP or no
EPP, f/b RT
• no difference in OS at 6, 12, or
18 months

11. EPP vs P/D
• Largest series of 663 consecutive
pts
• Operative mortality was greater for
EPP than for P/D (7% vs 4%)
• EPP was associated with a worse
OS (median: 12 vs 16 months)

12. MARS 2
• Aim: Compare clinical and cost-effectiveness of (extended) P/D and
chemotherapy vs chemotherapy alone for pts with pleural mesothelioma
• Primary outcome - OS -> to test the hypothesis that (extended) P/D and
chemotherapy is superior (30% relative improvement) to chemotherapy alone
• Sample size of 328 participants (alpha 0.05, power 0.80)
• Secondary outcomes: PFS, safety, HRQoL (EORTC, EQ5D), cost
effectiveness

13. Slide Courtesy: WCLC 2023

14. Results
Slide Courtesy: WCLC 2023

15. Results
Slide Courtesy: WCLC 2023

16. Slide Courtesy: WCLC 2023

17. Slide Courtesy: WCLC 2023

18. Slide Courtesy: WCLC 2023

19. Slide Courtesy: WCLC 2023

20. Slide Courtesy: WCLC 2023

21. Slide Courtesy: WCLC 2023

22. Slide Courtesy: WCLC 2023

23. Author’s conclusions
Slide Courtesy: WCLC 2023

24. Role of RT
• Data from retrospective series show addition of RT following EPP or P/D
improves local control but not OS
• Treating the entire pleura requires a large radiation field, which increases the
risk of toxicity
• IMRT allows more effective sparing of normal tissues -> lesser toxicity and
increased efficacy by enabling higher doses to the target
• Majority of local failures occur at sites of gross disease -> supporting the role
of MCR
• Ongoing trial: NRG-LU006

25. Target volume

26. 95% Dose Coverage

27. 50% Dose coverage

28. Take Home Message
• Rare tumor - generally present with locally extensive disease - poor
prognosis
• Chemotherapy remains the mainstay of treatment
• Surgery, RT and systemic chemotherapy may be beneficial in carefully
selected pts
• For pts being considered for combined modality t/t - attempt MCR
• For non-surgical candidates -> systemic therapy and/or symptom-
directed t/t

29. Acknowledgement: Dr. Anil Tibdewal