Rucaparib in refractory pleural mesothelioma harboring somatic pathogenic BRCA1 and BRCA2 mutation. A report of two cases

Our plain-English summary of Rucaparib in refractory pleural mesothelioma harboring somatic pathogenic BRCA1 and BRCA2 mutation. A report of two cases, by L. Cerbone, B.D. Rio, S. Delfanti, et al (Lung Cancer Management, 2025).

The study

• Authors: L. Cerbone, B.D. Rio, S. Delfanti, F. Boccuzzi, P. Barbieri, A.M. De Angelis, S. Meda, L. Savi, L. Righi, M. Sculco, I. Dianzani, P. Bironzo, F. Grosso
• Journal: Lung Cancer Management
• Published: 2025;14(1):2424133
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma is a rare disease with few therapeutic options, especially in the first line refractory setting. Targeted agents did not demonstrate a significant clinical benefit in mesothelioma treatment, nevertheless a small group of patients might harbor potentially actionable somatic mutations, as in homologous repair recombination genes. In this paper we report two cases of patients with heavily pretreated pleural mesothelioma that had a relevant clinical benefit with rucaparib treatment based on somatic BRCA 1 and BRCA 2 mutations detected through next generation sequencing.

In plain English

This case report described two women in Italy whose pleural mesothelioma progressed despite several earlier treatments. The first, a 55-year-old nonsmoker with occupational asbestos exposure, was diagnosed with epithelioid right pleural mesothelioma in March 2018. The second, a 51-year-old nonsmoker with known environmental asbestos exposure, presented in May 2019 with epithelioid pleural mesothelioma. Tumor testing found a somatic BRCA2 mutation in the first and a pathogenic BRCA1 mutation in the second. Both then received rucaparib off-label, outside its approved uses. In the first, pain resolved, opioids were stopped and CT showed a partial response in all known disease sites. Her disease later progressed, and she died in July 2022. In the second, daily oxycodone fell from 50 mg to 5 mg, a CT scan showed stable disease with less pleural effusion, and a later PET-CT showed a metabolic response. She was alive in February 2024. Both had a progression-free interval of around 8 months. The authors reported rucaparib was well tolerated and concluded that, within a multidisciplinary tumor board discussion, it might be a viable option for such patients.

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: Case report (case series of two patients)
• Who was studied: Two women with heavily pretreated epithelioid pleural mesothelioma treated at a hospital in Alessandria, Italy. One was a 55-year-old nonsmoker diagnosed in March 2018. The other was a 51-year-old nonsmoker who presented in May 2019.
• Exposure: Asbestos exposure was occupational for patient 1 and environmental for patient 2. No fiber type was given. The treatment studied was off-label single-agent rucaparib, a PARP inhibitor, given because of somatic BRCA1 or BRCA2 mutations found by next-generation sequencing.
• Main results:
  • Patient 1: sequencing of the surgical specimen found a somatic BRCA2 mutation (variant allele fraction 4.84%; p.Met2235fs*4). Germline testing did not find this mutation in the germline genome.
  • Patient 1: started fifth-line rucaparib in August 2021. Pain fully resolved, opioid painkillers were withdrawn, and a CT scan showed a partial response in all known disease sites. Rucaparib was stopped at multisite progression in May 2022. The patient died in July 2022 after abemaciclib and best supportive care.
  • Patient 2: sequencing of a flank mass biopsy found a pathogenic BRCA1 mutation (Q1779*, 6.77% variant allele fraction) and a class II BRAF variant (D287N, 4.87% variant allele fraction).
  • Patient 2: after starting rucaparib in February 2022, daily oxycodone fell from 50 mg to 5 mg. The article reports no toxicity above grade 3.
  • Patient 2: a CT scan showed stable disease with reduced pleural effusion, and a later PET CT scan showed a metabolic response. Rucaparib continued until progression in November 2022.
  • Patient 2 was still alive, in good general condition and off therapy, as of February 2024.
  • Both patients had a progression-free interval of around 8 months, which the authors described as unprecedented in pretreated pleural mesothelioma.
  • Rucaparib was well tolerated in both patients and did not require any treatment interruption for intolerable toxicity.
• The authors' conclusion: The authors concluded that single-agent rucaparib, considered within a multidisciplinary tumor board discussion, might be a viable option for pleural mesothelioma patients with somatic pathogenic mutations in BRCA1 or BRCA2, with no significant added toxicity.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Somatic Mutation.

Related studies

• Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations — M.G. Zauderer, M. Bott, et al. (2013)
• Malignant STK11 adnexal tumor harboring a somatic mutation in a woman previously diagnosed with mesothelioma, a case report — C.R. Rutherford, T.A. Rives, et al. (2024)
• Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial — D.A. Fennell, A. King, et al. (2021)
• A Prospective Phase II Single-arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non-small-cell Lung Cancer and/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design — F. Passiglia, P. Bironzo, et al. (2021)
• A study of somatic BRCA variants and their putative effect on protein properties in malignant mesothelioma — K. Krishnamurthy, K.S. Oh, et al. (2023)
• Estimating Cancer Penetrance in Carriers of BRCA2 Pathogenic Variants Using Cancer-Specific Polygenic Scores — B. Prassas, Z. Shi, et al. (2025)

Browse return to medical research.