96IN - Clinical interpretation of response with immunotherapy

Date 28 September 2014
Event ESMO 2014
Session Evasion, activation and manipulation of the cancer immuno response
Topics Cancer Immunology and Immunotherapy
Presenter Jan Haanen
Citation Annals of Oncology (2014) 25 (suppl_4): iv35-iv35. 10.1093/annonc/mdu311
Authors J.B.A.G. Haanen
  • Medical Oncology, The Netherlands Cancer Institute, NL-1066 CX - Amsterdam/NL

Abstract

Body

Abstract:

In the past 4 years immunotherapy of cancer has become an approved strategy for the treatment of human cancer. Sipuleucel-T was approved for CRPC (1) and ipilimumab has been approved for the treatment of MM (2,3). Because of very promising results with PD1/PD-L1 blockade in MM, mRCC and NSCLC, chances that these drugs will become approved in the near future are high(4-6). Targeting CTLA4 or PD1/PD-L1 work at the interaction between antigen presenting cells or tumor cells and T-cells. This may shift the balance from an ineffective to an affective T-cell immune response. Whereas for classical cytotoxic drugs and targeted agents objective response rates and progression free survival indicate the efficacy of the treatment, this is much less the case for immunotherapy. The major benefit for immunotherapy lies in inducing long-term responses (CR, PR and SD) in patients. These responses can develop over prolonged periods of time, and patients may show disease progression early on, followed by regression or disease stabilization later. Therefore, the classical criteria to measure responses (RECIST or WHO) sometimes fail to assess the clinical benefit patients experience from immunotherapy. Based on this short-coming, immune-related Response Criteria (irRC) have been proposed that allow continuation of treatment in clinical trials despite signs of unresponsiveness or mixed effects at first evaluation. The currently so oftentimes demonstrated swimmer plots for PD1/PD-L1 blockade demonstrate that objective responses can develop over time (7). By stopping treatment too early, the postponed clinical responses observed in patients treated with immunotherapy, may be missed, depriving the patients from a potentially effective or even durable disease remission. In conclusion, clinical interpretation of response to immunotherapy requires the implementation of specific immune related response criteria to allow continuation of treatment beyond early disease progression. 1. Kantoff PW, et al. N Engl J Med. 2010;363:411–22. 2. Hodi FS, et al. Engl J Med. 2010;363:711–23. 3. Robert C, et al. N Engl J Med. 2011;364:2517–26. 4. Topalian SL, et al. N Engl J Med. 2012;366:2443–54. 5. Brahmer JR, et al. N Engl J Med. 2012;366:2455–65. 6. Hamid O, et al. N Engl J Med. 2013;369:134–44. 7. Wolchok JD, et al. Clin Cancer Res 2009;15:7412–20.

Disclosure:

J.B.A.G. Haanen: Received research grant from BMS Consultancy role for BMS, Merck, Roche, GSK.