Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers

Our plain-English summary of Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers, by A. Parisi, F. Rossi, C. De Filippis, et al (OncoTargets and Therapy, 2023).

The study

• Authors: A. Parisi, F. Rossi, C. De Filippis, F. Paoloni, C. Felicetti, A. Mammarella, F. Pecci, A. Lupi, R. Berardi
• Journal: OncoTargets and Therapy
• Published: 2023;16:585-613
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In recent years, poly (ADP-ribose) polymerase (PARP) inhibition has become a promising therapeutic option for several tumors, especially for those harboring a BRCA 1-2 mutation or a deficit in the homologous recombination repair (HRR) pathway. Nevertheless, to date, PARP inhibitors are still not largely used for thoracic malignancies neither as a single agent nor in combination with other treatments. Recently, a deeper understanding of HRR mechanisms, alongside the development of new targeted and immunotherapy agents, particularly against HRR-deficient tumors, traced the path to new treatment strategies for many tumor types including lung cancer and malignant pleural mesothelioma. The aim of this review is to sum up the current knowledge about cancer-DNA damage response pathways inhibition and to update the status of recent clinical trials investigating the use of PARP inhibitors, either as monotherapy or in combination with other agents for the treatment of thoracic malignancies. We will also briefly discuss available evidence on Poly(ADP-Ribose) Glycohydrolase (PARG) inhibitors, a novel promising therapeutic option in oncology.

© 2023 Parisi et al.

In plain English

This article was a review, not a new study. The authors summarized laboratory research and clinical trials of PARP inhibitors, drugs that block a DNA-repair enzyme, used alone or with chemotherapy, radiotherapy, immunotherapy or other drugs in non-small cell lung cancer, small cell lung cancer and malignant pleural mesothelioma. They also discussed PARG inhibitors. Asbestos was not studied; it appeared only where the review, citing earlier work, said some mesothelioma patients with inherited DNA-repair gene mutations had shown sensitivity to asbestos. For mesothelioma, the review described an earlier olaparib trial in 23 patients. Median progression-free survival was 2.3 months (95% confidence interval 1.3 to 3.6) in patients with inherited BAP1 mutations and 4.1 months (2.7 to 5.5) in those with tumor-only (somatic) BAP1 mutations. Ongoing trials listed included one covering both pleural and peritoneal mesothelioma. In non-small cell lung cancer, trials of PARP inhibitors alone had not shown improved outcomes. The authors concluded that single-agent effectiveness in thoracic cancers still needed to be shown, and noted no clinical trial had yet shown benefit from PARG inhibitors.

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: Narrative review of preclinical studies and published and ongoing clinical trials (no new data collected; no search method described)
• Who was studied: Studies and trials in patients with small cell lung cancer, non-small cell lung cancer and malignant pleural mesothelioma, plus laboratory (cell line and animal) studies
• Exposure: Treatment with PARP inhibitors (e.g. olaparib, niraparib, rucaparib, talazoparib, veliparib, iniparib) alone or combined with other therapies; PARG inhibitors also discussed. Asbestos exposure was not an exposure studied.
• Main results:
  • Citing an earlier study, the review states that a percentage (5–10%) of patients with malignant pleural mesothelioma with germline mutations in DNA damage repair genes have shown a relevant sensitivity to asbestos
  • The review describes an earlier phase 2 single-center trial (Ghafoor et al) of olaparib in 23 patients with advanced malignant pleural mesothelioma with somatic or germline DNA repair gene mutations
  • In that earlier olaparib trial, as reported by the review: in germline and somatic BAP1 mutants, median progression-free survival was 2.3 months (95% CI 1.3–3.6) versus 4.1 months (95% CI 2.7–5.5), and median overall survival was 4.6 months (95% CI 3.1–4.9) versus 9.6 months (95% CI 5.5 months to not estimable), p=0.0040
  • The ongoing TALAMESO trial of talazoparib includes patients with advanced malignant pleural mesothelioma (cohort A) or peritoneal mesothelioma (cohorts B1 and B2)
  • In small cell lung cancer, olaparib maintenance after first-line treatment showed no significant progression-free or overall survival benefit among the 220 patients in the STOMP trial
  • In non-small cell lung cancer, trials of PARP inhibitors as monotherapy did not show improved outcomes
  • No clinical trial had yet shown benefit from PARG inhibitors
• The authors' conclusion: The authors concluded that PARP inhibitors face resistance and side effects, and that their efficacy as single agents in thoracic malignancies still needs to be fully demonstrated

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Lung Cancer, Pleural Mesothelioma, Clinical Trial.

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