USA – Determining the Clinical Benefit of Treatment Beyond Progression with Immune Checkpoint Inhibitors

In 2018, James Allison and Tasuku Honjo won the Nobel Prize in Physiology or Medicine for their work leading to the development of immune checkpoint inhibitors, a type of cancer drug that blocks certain proteins made by some types of immune cells.1 Their breakthrough underscores how the ability to manipulate the human immune system has transformed cancer treatment (Figure 1). These drugs have led to dramatic responses in several advanced cancers, including metastatic melanoma, lung cancer, kidney cancer, bladder cancer, and head and neck cancers.

However, in some patients, these drugs do not shrink the tumors or reduce tumor growth, and these patients may need to undergo alternative treatments. Moreover, approximately 4 percent of patients with solid tumors treated with immune checkpoint inhibitors demonstrate “pseudoprogression,” meaning that imaging data show initial tumor growth followed by tumor shrinkage.2

Pseudoprogression complicates decision-making for clinicians who treat patients and for regulators who specify indications for these drugs. Some oncologists continue to treat patients even when imaging data indicates that the tumor has progressed. This is called “treatment beyond progression.” However, the clinical benefit of treatment beyond progression is unknown, and the approach carries some risks:

  • Delay of administration of an alternative, potentially effective therapy
  • Safety issues associated with continuing treatment with immune checkpoint inhibitors, such as immune-related adverse events…