Advancing real-world research in thoracic malignancies: learnings from the international I-O Optimise initiative

Our plain-English summary of Advancing real-world research in thoracic malignancies: learnings from the international I-O Optimise initiative, by S.P. Johnsen, P. Baas, J.B. Sørensen, et al (Future Oncology, 2025).

The study

• Authors: S.P. Johnsen, P. Baas, J.B. Sørensen, C. Chouaid, F. Griesinger, M.J. Daumont, C. Rault, G. Emanuel, J.R. Penrod, H. Jacobs, M. Muwaffak, M.J. Schoemaker, R.E. Munro, D. Baskaran, I. Durand-Zaleski, J.C. O'Donnell
• Journal: Future Oncology
• Published: 2025;21(7):867-878
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In recent years, the thoracic malignancies treatment landscape has become more complex with the emergence of novel targeted and immunotherapy-based treatments. Although beneficial to patients and physicians, this fast-paced therapeutic evolution has increased the complexity of clinical decision-making and amplified the importance of real-world evidence to support data from randomized controlled trials. The international I-O Optimise initiative was established in 2016 to provide real-world insights into the thoracic malignancies treatment landscape, and has since collaborated with 14 data sources across Europe and Canada, allowing access to data from ~ 500,000 patients with non-small-cell lung cancer, small-cell lung cancer, and malignant pleural mesothelioma. This article reviews pertinent I-O Optimise research, with discussion of the methodological/data-related learnings and expectations for future insights.

In plain English

This article was a review of research produced by the I-O Optimise initiative, a program that used existing real-world data sources to study thoracic cancers: non-small-cell lung cancer, small-cell lung cancer, and malignant pleural mesothelioma (MPM). The initiative worked with 14 data sources in nine European countries and Canada, covering about 500,000 patients. The article did not study asbestos exposure. For MPM, the review described an English registry analysis of about 9500 patients diagnosed from 2013 to 2017. In that analysis, 60% received only best supportive care or palliative radiotherapy, with a median overall survival of 4.6 months. Another 33% received systemic anticancer therapy, with a median of 14 months, and 7% had surgery, with a median of 17 months. A Danish study of patients diagnosed from 2011 to 2018 reported median survival of 10.0 months for advanced MPM and 18.0 months for non-advanced MPM. The authors noted that some analyses could not establish cause and effect. They also noted that rare cancers such as MPM made it hard to find large enough patient groups. The authors concluded that high-quality real-world data are still needed to inform clinical and regulatory decisions.

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: Review of studies conducted within the I-O Optimise real-world research initiative
• Who was studied: Patients with non-small-cell lung cancer, small-cell lung cancer or malignant pleural mesothelioma in 14 real-world data sources covering about 500,000 patients in nine European countries (Denmark, England, France, Germany, Italy, Norway, Portugal, Spain, Sweden) and Canada, with data from 2005 onward
• Exposure: Asbestos exposure was not studied. The reviewed research concerned cancer treatments (immunotherapy, targeted therapy, chemotherapy, surgery, radiotherapy) and outcomes.
• Main results:
  • In an English nationwide registry (CAS) analysis of about 9500 patients diagnosed with MPM in 2013 to 2017, 60% received best supportive care or palliative radiotherapy alone (no surgery or systemic anticancer therapy)
  • In the English MPM analysis, best supportive care or palliative radiotherapy alone was associated with a median overall survival of 4.6 months
  • In the English MPM analysis, 33% received systemic anticancer therapy with or without radiotherapy (median overall survival 14 months) and 7% underwent surgery (median overall survival 17 months)
  • In the English MPM analysis, significantly worse prognosis was associated with older age (65 or more vs 18 to 64 years), worse ECOG performance status (2 or more vs 0 to 1), and non-epithelioid histology (sarcomatoid, biphasic and 'not otherwise specified' vs epithelioid)
  • In a Danish study (SCAN-LEAF) of adults newly diagnosed with MPM in 2011 to 2018, among patients with known stage, 54% of those with advanced MPM (n = 390) and 46% of those with non-advanced MPM (n = 325) had no recorded treatment within 6 months of diagnosis
  • In the Danish MPM study, median overall survival was 10.0 months for advanced MPM and 18.0 months for non-advanced MPM
  • In the Danish MPM study, age 75 or more at diagnosis (vs under 65), sarcomatoid or unspecified histology (vs epithelioid), and stage IV disease (vs all other stages) were associated with an increased risk of mortality
  • According to the authors, MPM data from the CAS database were used in regulatory submissions to the UK National Institute for Health and Care Excellence, which led to a marketing authorization for nivolumab plus ipilimumab as first-line treatment of unresectable MPM
  • Among referred patients with advanced non-small-cell lung cancer at a Portuguese single-site oncology hospital, the treatment rate was 76%, compared with about 30% in the broader English REAL-Oncology data source
  • In 227 (Portugal) and 425 (England) patients with small-cell lung cancer, around one-third did not receive systemic anticancer therapy, and their median overall survival ranged from 0.7 to 2.8 months
• The authors' conclusion: The authors concluded that, given rapidly emerging new therapies, high-quality real-world data are still needed to inform clinical and regulatory decision-making. They stated that collaborating with existing data sources rather than running standalone prospective studies saved time and cost.
• Limitations the authors state:
  • The Canadian and Frankfurt analyses were not designed to directly assess the relationship between immunotherapy uptake and survival, so causality could not be assigned
  • Small patient numbers in specific treatment or histology subgroups and relatively short follow-up limited some analyses
  • Because small-cell lung cancer and MPM are uncommon, it is often hard to identify large enough real-world patient populations for analysis
  • Baseline factors such as performance status, metastatic sites, comorbidities and smoking status were not available in all data sources
  • Privacy regulations made many data sources reluctant to share patient-level data, complicating analyses that combine more than one source

Topics

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

Related studies

• I-O Optimise: a novel multinational real-world research platform in thoracic malignancies — S. Ekman, F. Griesinger, et al. (2019)
• The Use of Radiation Therapy for the Treatment of Malignant Pleural Mesothelioma: Expert Opinion from the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation — D.R. Gomez, A. Rimner, et al. (2019)
• COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study — M.C. Garassino, J.G. Whisenant, et al. (2020)
• Antibody drug conjugates in thoracic malignancies — J.M. Pacheco, D.R. Camidge (2018)
• The efficacy of immune checkpoint inhibitors in thoracic malignancies — J. Remon, F. Facchinetti, et al. (2021)
• Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: state of the art and future perspectives — F. Petrella, I. Rimoldi, et al. (2018)

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