PROs Represent a Vital Aspect in Design of GI Cancer Clinical Trials

Incorporating patient-reported outcomes (PROs) as a measurement of success in clinical trials, supplementary to measuring adverse effects (AEs), continues to be an area of great interest, across the gastrointestinal (GI) cancer landscape, and as clinical trials continue to evolve, it remains important to make sure that the patient’s voice is heard throughout their treatment, according to Pamela Kunz, MD.

“[We must] emphasize to patients that they're the center of clinical research and that we anchor what we do on partnering with patients,” Kunz explained. “Their input will help affect future treatments that are available to patients.”

In an interview with OncLive^® News Network: On Location during the 2023 ASCO Annual Meeting, Kunz detailed key clinical trial updates across the GI cancer arena presented during the conference, including the phase 3 PROSPECT trial (NCT01515787) in locally advanced rectal cancer and the phase 3 IMbrave050 trial (NCT04102098) in patients with resected in hepatocellular carcinoma (HCC) at high risk of recurrence. She also explained the continued importance of utilizing PROs in clinical trials and emphasized the significance of improving diversity, equity, and inclusion.

Kunz is an associate professor of internal medicine, Medical Oncology, chief of GI Medical Oncology, vice chief of Diversity, Equity, and Inclusion, Medical Oncology, and director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, Yale School of Medicine, in New Haven, Connecticut.

OncLive: What were you most looking forward to seeing the results of at this year’s 2023 ASCO Annual Meeting?

Kunz: I always love coming to ASCO, and I was really excited to see the results of some of the randomized studies, specifically PROSPECT, which is a plenary. I [was also] really excited to see the incorporation of more thought around patient health equity and diversifying our clinical research.

Starting with IMbrave050, why do you believe this study has garnered such a high amount of attention?¹

IMbrave050 is a randomized study for patients with resected HCC at high risk of recurrence. Investigators randomly assigned patients to receive atezolizumab [Tecentriq] plus bevacizumab [Avastin] vs best supportive care. That combination is used in the first-line metastatic setting, so they were bringing that earlier to see if it could reduce the risk of recurrence, and it did.

[Data showed] both a statistically significant and clinically meaningful difference in recurrence-free survival for this group of patients. [This study] will be practice changing. This principle of bringing the best treatments to the earlier setting to benefit patients is critically important.

IMbrave050 also included PROs, and they demonstrated no difference in health-related quality of life. Incorporating these PROs are far better than us as investigators grading AEs. We're seeing a real movement to including the patient's voice.

Could you expand more on the PROSPECT trial?²

PROSPECT was a randomized trial of patients with locally advanced rectal cancer and looked at this question of [omitting] radiation. At the time that study was designed, chemotherapy with 5-fluorouracil and radiation was the standard of care prior to surgery. We saw that the results demonstrated that you could safely omit to radiation in select patients with locally advanced rectal cancer and there was no difference compared with chemotherapy alone.

The New York Times picked this up, and there were then some comments around how we discussed and described risks of radiation. The takeaway from the PROSPECT study is that the field has changed since that trial was first designed. We are learning that de-escalation of therapy—no matter what you've removed—[has questions that come with it], whether it's reducing the amount of chemotherapy, omitting surgery, or [removing] radiation for high rectal cancer. At the 2022 ASCO Annual Meeting, we learned that in a select group of patients with microsatellite instability–high rectal cancer, you can treat with immunotherapy alone.

The field is changing. This idea of de-escalating therapy, whether we can remove any of those components, will be better for our patients. What The New York Times picked up on was that, yes, there can be AEs from radiation, but there can be AEs from all of these [treatments]. As a multidisciplinary field, we need to think about how we can improve quality of life for our patients by removing any of these therapies.

[This study] also include PROs, and [findings] demonstrated that the PROs are improved by removing radiation.

What about gastric/gastroesophageal cancer? What are we seeing in that space?

There were not a lot of practice changing data [for this patient population]. However, there was a great presentation on PROs that were incorporated into some studies. It was a great overview of how we think about PROs and the importance of incorporating those into clinical trials.

Looking back to PROSPECT, the discussant for this trial included a patient slide, discussing how outwardly, a patient may look okay, but it's important to ask them what they're experiencing [and] including that patient voice in what we do.

Another important element of this year's meeting was the importance of diversity, equity, and inclusion. What are we seeing in that arena?

There are 2 ways of thinking about diversity. We can think about workforce diversity. We want our physicians, nurses, and research staff to reflect the patients we serve. We need to do a better job of that. For example, only 3% of the oncology workforce is Black, yet 13% of the United States population is Black.

If we think about the benefits of diversity—improving the creativity and innovation of our science—we can then also think about how that translates into helping health equity for our patients. There have been a lot of conversations about improving our clinical trials to be more representative and inclusive of all patients, and how to increase accrual of our underrepresented minority patients and remove barriers to trial. There was a great session that was co-sponsored by ASCO, the FDA, and the National Cancer Institute on how to revolutionize clinical trials to meet a lot of those needs.

Some studies have been limited by the collection of PROs, as some patients submit them in the beginning, and then they drop off. What can be done to improve responsiveness to PROs?

It's hard, and we need to make it easier for patients. There's a new philosophy talking about time toxicity for patients, [meaning] the amount of time it takes for them to participate in clinical trials or routine clinical cancer care. We sometimes need to factor that into what we ask of our patients. Do we need to compensate them for travel? Do we need to pay for childcare? There are a lot of ways that we need to improve what we ask of our patients, in terms of making [clinical trial participation] easier for them.

References

1. Kudo M, Chen M, Chow PKH, et al. Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. J Clin Oncol. 2023;41(suppl 16):4002. doi:10.1200/JCO.2023.41.16_suppl.4002
2. Schrag D, Shi Q, Weiser MR, et al. PROSPECT: a randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC) (Alliance N1048). J Clin Oncol. 2023;41(suppl 17):LBA2. doi:10.1200/JCO.2023.41.17_suppl.LBA2