Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications

Our plain-English summary of Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications, by L. Calabrò, R. Danielli, L. Sigalotti, et al (Seminars in Oncology, 2010).

The study

• Authors: L. Calabrò, R. Danielli, L. Sigalotti, M. Maio
• Journal: Seminars in Oncology
• Published: 2010;37(5):460-7
• Type of article: Review
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Available medical treatments have limited impact on the survival of patients with advanced cancer; therefore, new therapeutic strategies able to generate more effective host's immune responses against neoplastic cells are being actively pursued. Among these, a recent approach involves targeting of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key immune checkpoint molecule, by monoclonal antibodies (mAbs). Ipilimumab and tremelimumab represent the prototypes of this new class of immunomodulating mAb and have been extensively tested in metastatic melanoma with highly promising results. The clinical activity observed in melanoma has served as a model to exploit the therapeutic potential of CTLA-4 blockade in a variety of human malignancies. Along this line, early-phase trials with anti-CTLA-4 mAbs have been completed or are ongoing in tumors of different histotype. Results are demonstrating the feasibility, safety, and activity of these agents, thus suggesting a promising therapeutic role to be further investigated in phase II/III trials in a wide range of tumors. This review summarizes the main trials with ipilimumab and tremelimumab in tumors of different histotypes, excluding cutaneous melanoma, which is extensively described in other chapters of this issue of Seminars in Oncology.

Copyright © 2010 Elsevier Inc. All rights reserved.

In plain English

This was a review. The authors summarized early-phase clinical trials, completed or ongoing, of two antibody drugs, ipilimumab and tremelimumab, in cancers other than cutaneous melanoma. Both drugs block an immune checkpoint molecule called CTLA-4. The article did not discuss asbestos. One short section covered malignant mesothelioma. It described an ongoing phase II trial at a single institution of tremelimumab as second-line treatment for patients with unresectable malignant mesothelioma whose disease had progressed during or after first-line platinum-based chemotherapy. That trial planned to enroll 29 patients. From May 2009 to June 2010, 11 patients with stage III or IV disease (seven males, four females) had been enrolled. The review reported no results from that trial. The review also covered trials in lung, prostate, kidney, bladder, breast, digestive and other cancers. The authors concluded that early-phase trials had shown anti-CTLA-4 antibody treatment to be feasible, safe and effective in a wide range of cancers, and that it should be investigated further in phase II/III trials.

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 clinical trials (many reported only as meeting abstracts or trial registrations)
• Who was studied: Clinical trials of anti-CTLA-4 antibodies in patients with tumors other than cutaneous melanoma, including ocular melanoma, lung cancer, malignant mesothelioma, prostate, renal, bladder, breast, gastroesophageal, colorectal and pancreatic cancers, and others
• Exposure: Not an asbestos exposure study. The treatments reviewed were the anti-CTLA-4 monoclonal antibodies ipilimumab and tremelimumab, alone or combined with other therapies
• Main results:
  • Mesothelioma: an ongoing phase II, single-institution trial gave tremelimumab as second-line therapy to patients with unresectable malignant mesothelioma.
  • Mesothelioma trial: planned enrollment was 29 patients whose disease had progressed during or after first-line platinum-based chemotherapy.
  • Mesothelioma trial: from May 2009 to June 2010, 11 patients with stage III or IV malignant mesothelioma (seven males, four females) had been enrolled and had received at least one dose. No outcome results were reported.
  • Advanced non-small cell lung cancer (Zatloukal et al): in maintenance therapy, tremelimumab did not show superior progression-free survival over best supportive care. The response rate in the tremelimumab arm was 4.8%.
  • Metastatic uveal melanoma (Danielli et al, 13 patients given ipilimumab): no objective tumor responses were observed.
• The authors' conclusion: The authors concluded that early-phase trials had shown anti-CTLA-4 antibody treatment, across a range of doses and schedules, to be feasible, safe and effective in a wide range of malignancies, and that it should be investigated further in phase II/III trials.
• Limitations the authors state:
  • The authors noted that standard tumor-response criteria may not adequately capture the responses seen with anti-CTLA-4 antibodies, so future studies need new immune-related response criteria.

Topics

Medical terms in this study, explained in our Lexicon: CTLA-4, Monoclonal, Ipilimumab (Yervoy), Tremelimumab.

Related studies

• Anti-CTLA-4 therapy for malignant mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy? — L. Calabrò, G.L. Ceresoli, et al. (2015)
• Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial — L. Calabrò, A. Morra, et al. (2013)
• Tremelimumab for the treatment of malignant mesothelioma — A. Guazzelli, M. Hussain, et al. (2015)
• Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study — L. Calabrò, A. Morra, et al. (2018)
• Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study — L. Calabrò, A. Morra, et al. (2015)

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