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Targeted PRO Tools Needed to Evaluate QOL in Immuno-Oncology Trials


A review published in Cancer examines the efficacy and drawbacks of tools used to evaluate health-related quality of life in immuno-oncology clinical trials.

A review published in Cancer examines the current state of the tools used to evaluate health-related quality of life (HRQOL) in oncological trials, highlighting the efficacy and drawbacks of those tools when applied to patients with solid-tumor cancers undergoing immunotherapy. Given the high cost and potential toxicities of immunotherapy in these patients, developing and validating targeted and effective tools to evaluate HRQOL over the course of therapy in those patients should remain a priority, the authors wrote.

While immuno-oncology (IO) therapies have become a cornerstone in some cancer types and have undoubtedly improved traditional study end points in terms of survival, immune-related adverse events (irAEs) are a common effect of IO agents that can significantly affect HRQOL during and after therapy. Therefore, the authors stress the importance of adequate risk-benefit assessments to ensure that “meaningful and valuable” IO therapies are approved for the treatment of cancer and noted that unlike AEs that typically occur during treatment with other agents like chemotherapy, irAEs do not necessarily have a dose-response or dose-toxicity relationship.

“An evaluation of the benefit of these IO agents must include a determination of their effects on HRQOL to ascertain the real value of the treatments beyond traditional statistically significant efficacy,” they wrote. “HRQOL is a complex, abstract, and multidimensional idea that describes an individual’s satisfaction with life in the domains considered most vital.” This encompasses measures like general health (defined in the review as physical, social, and psychosocial health), as well as cancer- and therapy-related effects like symptoms and side effects.

The review introduces patient-reported outcomes (PROs), which have become increasingly common in cancer clinical trials, as a key element of successful HRQOL assessment in patients on IO with solid tumors. Examples of oncology-specific PRO tools are the Functional Assessment of Cancer Therapy-General (FACT-G) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Both have been extensively validated, are familiar to most researchers, and are available in multiple languages.

The PRO adaptation of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (PRO-CTCAE) has helped with collecting data on symptomatic AEs, although it was initially developed for either surgery, radiation, and/or chemotherapy—not IO therapy, which has additional relevant AEs— according to the study authors.

Despite the existence of these tools for cancer in general, authors raise the question of whether they are sufficiently sensitive to effectively monitor the HRQOL of patients undergoing IO treatment for cancer. The inclusion of symptomatic irAEs in such tools is paramount if they are used to monitor this patient population. And despite the differences between IO therapy and more traditional treatments, many trials utilize conventional HRQOL tools and consider HRQOL a secondary or exploratory end point, according to the review. Those are both limitations in gauging quality of life over the course of treatment and for risk-benefit assessment of IO therapies.

“Currently, there is no widely adopted, validated instrument that has been tailored for this patient population, although a tool to measure HRQOL has been developed in patients receiving immune checkpoint modulators,” the authors wrote. There are 2 major issues in PROs for IO therapy clinical trials, they said:

  1. All the possible symptomatic irAEs from IO therapy need to be identified and translated into PRO items
  2. Patient input is required to confirm that specific symptomatic irAEs impact HRQOL and then develop and validate tools or modules specific to the various classes of immunotherapies

The PRO-CTCAE, for example, does include items that that cover some of the more common irAEs—fatigue, rash, and pruritus. But some other common irAE symptoms—like tremors, neck swelling, muscle weakness, weight gain, shivering, or bleeding in stool—are not in the PRO-CTCAE item library. Although some efforts are underway to mitigate this knowledge gap, there is more work to be done, the authors concluded. That includes developing PRO tools for the new subsets of immunotherapy that are now being studied and added to the treatment armamentarium. Integrating PRO tools into early-phase trials to inform the development of tools for later studies will be key, they said.

“With the rising number of IO agents available, it has become clear that a more thorough understanding of irAEs is needed to generate a more complete picture of the risks and benefits associated with these treatments,” they wrote. “For this to occur, more comprehensive capturing of irAEs is required, and the effects of irAEs have on HRQOL must be evaluated. Efforts to develop these tools are underway and will be an important step forward in the understanding and accurate reporting of irAEs.”

Importantly, the HRQOL data collected from these trails will inform regulatory applications and ensure that new IO therapy approvals have undergone thorough risk-benefit and value analyses, ultimately affecting health care policy overall.


Voon PJ, Cella D, Hansen AR. Health-related quality-of- life assessment of patients with solid tumors on immuno-oncology therapies. Cancer. Published online March 4, 2021. doi:10.1002/cncr.33457

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