PRO in Pts With Rare Cancers: Pembrolizumab [2022]

Tito Mendoza, PhD, MS, MEd Speaks about PRO in Pts With Rare Cancers: Pembrolizumab [2022]


PRO in Pts With Rare Cancers: Pembrolizumab [2022]


Patient reported Outcome (PRO) in patients with rare cancers (rare diseases) treated with Pembrolizumab. Pembrolizumab's acceptability and safety are being investigated in this study. The clinical benefit grade, as well as the objective (objectively measured) response. This phase to study, which was published in the Journal For Immunotherapy of Cancer in 2020, showed that Pembrolizumab has a favorable toxicity profile and anti-tumor activity in patients (and their clinical care) with rare cancers (rare diseases) such as squamous cell carcinoma of the skin, carcinoma of unknown primary and adrenal cortical carcinoma, paraganglioma, and pheochromocytoma. However, the objective of this recent study, which was just released in the form of a scientific report, is to provide a rational description of how people with uncommon cancers (various diseases) feel and function while they are having cancer treatment with pembrolizumab which is increasingly important.


Can You Tell Us About Pembrolizumab?

The antibody that targets two different pathways, which is known as PD-L1, as well as the programmed cell death ligand (tumor cells). Or the programmed cell death ligand, often known as PD-L1, which is frequently misappropriated by tumor cells in order for them to circumvent immune monitoring.

It belongs to the class of medications known as cancer immunotherapies. Back in September of 2014, the FDA granted an expedited approval to pembrolizumab for the treatment of very advanced melanoma. Therefore, that was approximately 8 years ago. Since then, it has gained approval for the treatment of lung cancer caused by non-small cell. Clinical trials (Patient reported Outcome (PRO)) are currently being conducted on a wide variety of cancers, including squamous cell carcinoma of the head and neck and renal cell carcinoma, amongst others.


Have There Been Any Concerns With Risk to Adverse Events In Pembrolizumab In Rare Cancer(s)?

Pembrolizumab is administered intravenously or through an intravenous line, and these (normal biological) processes, it typically takes approximately half an hour. Depending on the patient, it may be administered once every 3 weeks or once every 6 weeks. And one of two places—a doctor's office or an infusion clinic—could serve as the venue for the procedure.


This is the only study that I am aware of in advanced-stage (rare) cancer patients that documented patient-reported symptom burden relatively regularly before patients had their initial illness evaluation. As far as I am aware, this study is the only one of its kind.


Tell Us About Patient-Reported Symptom Burdens For Patient reported Outcome (PRO)

The majority of studies that use patient reports as outcomes are planned with an evaluation of disease assessment occurring approximately 9 weeks after the treatment has been initiated. Throughout the first nine weeks of treatment in this clinical trial (Patient reported Outcome (PRO)), we carried out assessments on a weekly basis.

The National Cancer Institute and the Food and Drug Administration have both identified the requirement for more methodical approaches to the collection of patients' perspectives on the influence that (effective) treatments have had on how they feel and how well they are able to function.


There has also been a shift in the landscape of clinical trials toward early phase studies, where evidence from well-designed and pivotal phase 1 or 2 trials increasingly leads to faster medication approval. This shift in the landscape of clinical trials has been accompanied by a number of other changes. Investigations into toxicity and susceptibility are the primary focuses of early phase clinical trials. patient-reported results (clinical endpoint) concerning the effect that the treatment had on the individual.


The tumor would deepen our comprehension of the challenges faced by patients participating in these trials (Patient reported Outcome (PRO)). Therefore, it would be possible to conduct more rigorous and systematic (cancer) research if patient-reported outcomes were included in early phase trials. Evaluation of results based on information provided by patients in later phase trials.


Was There A Reason To Focus On Rare Cancer(s) In This Clinical Trial? (Patient reported Outcome (PRO))

There are, in fact, quite good reasons for this, despite the fact that each one is rather unusual. According to the clinical trial data from 2017, in the United States, rare cancers (rare diseases) combined accounted for 13% of all new (rare) cancer diagnoses and 25% of all (rare) cancer-related deaths in adults. This indicates that rare cancers pose a significant threat to the public's health.

Patients who have an advanced stage of a rare cancer (rare diseases) face the following prognosis: There are very few (cancer) research projects that have the potential to result in the creation and approval of new medicines for uncommon malignancies. As a consequence of this, it is necessary to discover effective therapeutic strategies in order to improve treatment outcomes in this patient population.


What Were Some Of The Patient-Reported Symptoms in Pts with Rare Cancer(s)?

Fatigue was the symptom that patients described as being the most severe after undergoing the treatment for a period of nine weeks. On a scale from 0 to 10, it was assessed to be approximately 3.8. On a scale that ranges from 0 to 10, the next most common symptom was pain, which was rated an average of 3.7.

This was followed by trouble sleeping at a score of 2.7, sleepiness at a score of 2.6, and a lack of appetite at a score of 2.5. Other symptoms include discomfort in the belly, which was weighted at 2.2, rush, which was weighted at 1.1, and diarrhea, which was weighted at 0.9, and these symptoms, as you can understand, were not as severe. The most significant factor was whether or not walking was hindered. On a scale that went from zero to ten, it was given a weight of 3.4.

However, patients' relationships with others and the ways in which those relationships affect them received the lowest rating of 2.1. In other words, in terms of how well people function, the most severe symptom is exhaustion, while rash and diarrhea are not nearly as severe as one might expect them to be. The patient's capacity to walk and their interactions with other people were the areas that were negatively impacted the most by these symptoms.


Please Highlight The Data From This Study On Patient reported Outcome (PRO)

Our group-based trajectory analysis reveals that there are subgroups of patients who have consistently high symptom burdens, despite the fact that the symptoms remain constant over the course of the first nine weeks of treatment.


Now, the percentage of these patients that have a high burden of symptoms shifts or varies based on the particular symptoms that are being experienced. We found (in the clinical data) that 42% of people have a high symptom burden when we looked at pain, exhaustion, lack of appetite, sleep disturbance, and feeling drowsy. When we looked at these factors, we came to this conclusion. But if we look at the symptoms that are specific to immunotherapy, such as rashes and diarrhea, the number drops to 33%. One question is.


What Are The Next Steps? (Patient reported Outcome (PRO))

We investigate whether there is a correlation between baseline demographic and clinical parameters and the severity of symptoms. However, those didn't produce any noteworthy findings (data). Therefore, factors such as age, gender, and performance status are examples of demographic variables. In addition, there is no correlation between them and the classification of symptom burden, which can be either high or low.

In a similar manner, we investigate the disparities in symptom ratings brought on by different treatment responses. To answer that question, we need to determine whether the patient has an objective (drug development process) response or not. According to those analyses, there is no noteworthy outcome to report. We most likely noticed that due to the small size of the sample, there are approximately 53 patients included in this patient sample.

The results of this investigation were, thus, generally inconclusive. As a result, we strongly advise that future studies use significantly higher sample sizes to determine demographics. And the clinical characteristics of patients who have a high symptom burden might make it possible to provide more individualized treatment for those symptoms.


What Were The Conclusions Of This Clinical Trial?

In a nutshell, our findings (data) indicate that it should be possible to collect patient-reported outcome data from patients who have unusual forms of (rare) cancer. Participating in a clinical trial (Patient reported Outcome (PRO)) of an immune checkpoint inhibitor either in its early phase or in its phase 2 stage in clinical settings. According to our research, the symptom trajectories of patients with (rare tumors (E.g. rare solid tumors)) uncommon malignancies who are being treated with pembrolizumab are shown to be relatively consistent over the course of the first nine weeks of treatment.

In addition, we discovered that the categorization of symptoms (Patient reported Outcome (PRO)) at the start of the study was not linked with any other demographic or clinical characteristics. Our findings (data) may offer doctors with information about the needs of symptom intervention and serve as a benchmark in the design of future clinical trials (Patient reported Outcome (PRO)) involving symptom intervention in clinical care.


Final Thoughts

So let me recap. Pembrolizumab, which is classified as an immune checkpoint inhibitor, was shown in a previous research to have both a favorable toxicity profile and anti-tumor effectiveness in patients with advanced uncommon cancers (E.g. rare solid tumors). This companion research to that early phase trial (Patient reported Outcome (PRO)) testing Pembrolizumab is focusing primarily on how patients feel and how well they are able to function while they are receiving therapy.

This research was carried out at the MD Anderson Cancer Center, which is affiliated with the University of Texas. However, this is very much in line with the aim of the newly founded office of patient-centered OPT outcomes research, whose mission it is to incorporate the patient's input in early phase trials being conducted by the Center for Cancer Research (and now with the National Cancer Institute). This mission was just just established.

Patients in this study were questioned regarding the intensity of their symptoms as well as the degree to which the symptoms hindered their ability to carry out their regular activities on a weekly basis.

Since they began treatment, we are aware of the symptoms that are the most severe as well as the ways in which they change over time.

We have high hopes that clinicians will find this material useful in the treatment of patients' symptoms. Help researchers design symptom intervention trials (Patient reported Outcome (PRO)), and give patients some idea of what to anticipate while they are undergoing treatment, if at all possible.


Tito Mendoza, PhD, MS, MEd - About The Author, Credentials, and Affiliations

The majority of Tito Mendoza's time is devoted to collaborative work utilizing his quantitative background in psychometrics and statistics to develop and evaluate the measurement properties of patient-reported outcomes (PRO)-based measurement questionnaires in the substantive field of cancer symptom research.

As a psychometrician, he contributed to the creation of single-symptom (Brief Fatigue Inventory) and multiple-symptom (MD Anderson Symptom Inventory, MDASI) evaluation instruments.

His collaborations with MD Anderson clinicians have led to the development of several disease-specific and cancer-site-specific modules of the MDASI, including the MDASI-Brain Tumor, the MDASI-Head and Neck, the MDASI-Thyroid, the MDASI-Gastrointestinal Cancer, and the MDASI-Heart Failure, among others. (And he as started collaborations with National Cancer Institute.) He also collaborates with our international partners to provide the appropriate theoretical measurement foundation for conducting validation of our assessment instruments in foreign languages.

Dr. Mendoza participated in multiple parts of the National Cancer Institute-funded development and validation of the patient-reported outcomes version of the Common Terminology Criteria Adverse Event (PRO-CTCAE). Currently, he is participating in the psychometric validation of PRO evaluation tools that are meant to satisfy the US Food and Drug Administration's mandate for the use of patient report in labeling claims.

Dr. Mendoza employs his statistical knowledge in the design, analysis, and interpretation of PROs investigations. Utilizing sophisticated statistical models to comprehend symptom outcomes (clinical outcome) is a key part of his study. He desires to determine how PROs might be utilized to establish and create responder-type assessments (pharmacologic responses) and affect clinical practice.

He is currently examining the symptom load of patients taking immune checkpoint inhibitors in combination with other cancer treatments. Now, Dr. Mendoza is a Senior Scientist/Psychometrician at the National Cancer Institute's Office of Patient-Centered Outcomes Research (OPCORe) Center for Cancer Research.