Five-year survival and clinical correlates among patients with advanced non-small cell lung cancer, melanoma and renal cell carcinoma treated with immune check-point inhibitors in Australian tertiary oncology centres

Our plain-English summary of Five-year survival and clinical correlates among patients with advanced non-small cell lung cancer, melanoma and renal cell carcinoma treated with immune check-point inhibitors in Australian tertiary oncology centres, by L.J. Brown, I.P. da Silva, T. Moujaber, et al (Cancer Medicine, 2023).

The study

• Authors: L.J. Brown, I.P. da Silva, T. Moujaber, B. Gao, R. Hui, H. Gurney, M. Carlino, A. Nagrial
• Journal: Cancer Medicine
• Published: 2023;12(6):6788-6801
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aims: There is robust trial evidence for improved overall survival (OS) with immunotherapy in advanced solid organ malignancies. The real-world long-term survival data and the predictive variables are not yet known. Our aim was to evaluate factors associated with 3-year and 5-year OS for patients treated with immune checkpoint inhibitors (ICIs).

Methods: We performed a retrospective study of patients who received ICIs as management of advanced solid organ malignancies in two tertiary Australian oncology centres from 2012-2017. Data pertaining to clinical characteristics, metastatic disease burden, immune-related adverse events (IRAEs) and tumour responses were collected and their relationship to survival examined.

Results: In this analysis of 264 patients, 202 (76.5%) had melanoma, 46 (17.4%) had non-small cell lung cancer (NSCLC), 12 (4.5%) had renal cell carcinoma (RCC) and 4 (1.5%) had mesothelioma. The 5-year OS rates were 42.1% in patients with melanoma, 19.6% with NSCLC, 75% with RCC, and none of the mesothelioma patients were alive at 5 years. In multivariate analysis, an ECOG score of 0 (Hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.23-0.66; p < 0.001) and the occurrence of IRAE's of any grade (HR 0.61; 95% CI 0.37-0.95; p = 0.05) were associated with better 5-year survival. The presence of bone metastases (HR 1.62; 95% CI 1.03-2.82; p = 0.05) and liver metastases (HR 1.76; 95% CI 1.07-2.89; p = 0.03) were associated with worse 5-year survival.

Conclusions: These results support the long-term benefits of immunotherapy that in some patients, extend to at least 5 years. ECOG performance status of 0 and the occurrence of irAEs are associated with better long-term survival. Survival is significantly influenced by metastatic site and cancer type. These predictive clinical correlates aid discussions and planning in the delivery of ICIs to patients.

© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

In plain English

This retrospective study did not examine asbestos exposure. It reviewed records of 264 patients with stage 4 cancer treated with immune checkpoint inhibitors between 2012 and 2017 at two Australian tertiary oncology centres. Of these, 202 had melanoma, 46 non-small cell lung cancer, 12 renal cell carcinoma and 4 mesothelioma. Five-year overall survival was 42.1% for melanoma, 19.6% for lung cancer and 75% for renal cell carcinoma. None of the 4 mesothelioma patients survived 3 years. Being few, with limited survival, they were excluded from the univariate and multivariate analyses. In multivariate analysis of the other 260 patients, an ECOG performance score of 0 and any immune-related side effect (hazard ratios 0.39, 95% CI 0.23 to 0.66, and 0.61, 95% CI 0.37 to 0.95) were associated with better 5-year survival. Bone and liver metastases at baseline (hazard ratios 1.62, 95% CI 1.03 to 2.82, and 1.76, 95% CI 1.07 to 2.89) were associated with worse 5-year survival. The authors concluded immunotherapy benefits extend to at least 5 years in some patients. They noted the retrospective design brings unavoidable selection bias.

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: Retrospective study of patient records from two centres; the authors describe the analyses as exploratory
• Who was studied: 264 patients with metastatic (stage 4) cancer treated at two Australian tertiary oncology centres, 2012 to 2017: 202 with melanoma, 46 with non-small cell lung cancer, 12 with renal cell carcinoma and 4 with mesothelioma (the article does not say whether pleural or peritoneal). The 4 mesothelioma patients were excluded from the univariate and multivariate analyses.
• Exposure: No asbestos exposure was studied. The exposure was treatment with immune checkpoint inhibitors: anti-PD1 monotherapy in 197 patients, ipilimumab in 23, and combination anti-PD1 plus ipilimumab in 44.
• Main results:
  • Five-year overall survival was 39.0% for the whole cohort, 42.1% for patients with melanoma and 19.6% for patients with non-small cell lung cancer (75% for renal cell carcinoma).
  • Among the 4 mesothelioma patients, 3-year overall survival was 0%. One of the 4 had a treatment response, and none had immune-related adverse events.
  • The mesothelioma patients were excluded from the univariate and multivariate assessments because of their small numbers and limited survival, which the authors considered likely driven by tumour factors.
  • In multivariate analysis (260 patients, mesothelioma excluded), an ECOG performance status of 0 versus 1 or more was associated with increased 5-year survival: HR 0.39 (95% CI 0.23 to 0.66; p less than 0.001).
  • In the same multivariate analysis, immune-related adverse events of any grade were associated with increased 5-year survival: HR 0.61 (95% CI 0.37 to 0.95; p = 0.05).
  • In the same multivariate analysis, metastases present at baseline were associated with reduced 5-year survival: bone metastases HR 1.62 (95% CI 1.03 to 2.82; p = 0.05) and liver metastases HR 1.76 (95% CI 1.07 to 2.89; p = 0.03).
  • Gender, BMI, smoking status, number of prior therapies, and lung, brain or lymph node metastases did not significantly influence 5-year overall survival.
• The authors' conclusion: The authors concluded that their results support enduring benefits of immunotherapy which, in some patients, extend to at least 5 years.
• Limitations the authors state:
  • The retrospective design is associated with unavoidable selection bias.
  • The sample size and heterogeneity of the cohort may influence the identification of predictive factors.
  • Small numbers of patients with renal cell carcinoma and mesothelioma mean some conclusions may reflect tumour type rather than the clinical factors studied.
  • Data were not available for a time-dependent analysis of immune-related adverse events, which other studies used to reduce survivor bias.

Topics

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

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Carcinoma, Overall Survival, Immunotherapy, checkpoint inhibitors, Immune-Related Adverse Events, Mesothelioma, Multivariate Analysis.

Related studies

• Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors — S. Hendry, R. Salgado, et al. (2017)
• A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies — C.C. Lin, E. Garralda, et al. (2024)
• Renal cell carcinoma — P.A. Godley, M.A. Escobar (1998)
• Carbonic anhydrase IX is expressed in mesothelioma and metastatic clear cell renal cell carcinoma of the lung — M.L. Ramsey, B.J. Yuh, et al. (2012)
• Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors — O.E. Rahma, K. Tyan, et al. (2022)
• The epidemiology of renal cell carcinoma — L. Lipworth, R.E. Tarone, et al. (2006)

Browse more research in Cancer Medicine, or return to medical research.