Symptom Burden and Blood Counts in Patients With Polycythemia Vera in the United States: An Analysis From the REVEAL Study

Background More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients’ perspectives on symptom burden and treatment toxicity. Methods PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients’ symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented. Results PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland. Conclusion The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.

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Patient-Reported Outcomes Data From REVEAL at the Time of Enrollment (Baseline): A Prospective Observational Study of Patients With Polycythemia Vera in the United States

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2018.05.020 ◽

2018 ◽

Vol 18 (9) ◽

pp. 590-596 ◽

Cited By ~ 5

Author(s):

Ruben Mesa ◽

Ralph V. Boccia ◽

Michael R. Grunwald ◽

Stephen T. Oh ◽

Philomena Colucci ◽

...

Keyword(s):

United States ◽

Observational Study ◽

Polycythemia Vera ◽

Patient Reported Outcomes ◽

Prospective Observational Study ◽

The United States ◽

Patient Reported

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Disease Characteristics of Minority Patient Populations with Polycythemia Vera: An Analysis from the Reveal Study

Blood ◽

10.1182/blood-2018-99-112530 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4735-4735 ◽

Cited By ~ 1

Author(s):

Ivy Altomare ◽

Philomena Colucci ◽

Shreekant Parasuraman ◽

Dilan Chamikara Paranagama ◽

Anas Al-Janadi

Keyword(s):

United States ◽

High Risk ◽

The United States ◽

Low Risk ◽

Employment Equity ◽

Disease Characteristics ◽

Reveal Study ◽

High Risk Disease ◽

Caucasian Patients ◽

Equity Ownership

Abstract Introduction: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. Few studies have examined the presence or absence of racial/ethnic disparities among patients with PV. The objective of this analysis is to describe differences in disease characteristics, diagnosis, treatment, and quality of life (QOL) among Caucasian and non-Caucasian patients with PV in the United States enrolled in the prospective, observational REVEAL study. Methods: The ongoing REVEAL study (ClinicalTrials.gov ID, NCT02252159) is a prospective, multicenter, observational study of adult patients with PV in the United States. Patients were observed during a 36-month period, during which clinical data were collected from usual care visits. This analysis compared demographics, disease and clinical characteristics, disease management, comorbidities, and QOL between Caucasian and non-Caucasian patients with PV at enrollment. QOL was measured by the European Organisation for Research and Treatment of Cancer Questionnaire C30 (EORTC QLQ-C30) and Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Results are summarized with descriptive statistics. Results: Of the 2,510 patients enrolled in REVEAL, 2,237 were Caucasian (89.1%); 199 (7.9%) were non-Caucasian, comprised of African American (5.7%), Asian (1.5%), Native American Indian (0.2%), Pacific Islander (0.1%), and other patients (0.4%); no information was provided regarding race or ethnicity for 74 patients (2.9%). Baseline disease characteristics were similar for Caucasian and non-Caucasian groups with respect to gender and disease duration. There were no differences in method of diagnosis, laboratory values, or overall history of thrombosis between groups (Figure 1A). Mean age was higher among Caucasian patients compared to non-Caucasian patients (66.6 vs 63.8 years, respectively). The proportion of patients from rural areas was higher among Caucasian vs non-Caucasian patients (28.8% vs 12.6%); similarly, the proportion of patients from urban areas was lower among Caucasian vs non-Caucasian patients (23.1% vs 46.7%). The proportion of patients with some college or higher level of education was higher among Caucasian vs non-Caucasian patients (64.1% vs 50.3%). A higher proportion of Caucasian vs non-Caucasian patients were retired (52.0% vs 43.2%); a higher proportion of non-Caucasian patients reported being unable to work or were disabled (3.8% vs 10.1%). More Caucasian patients had high-risk disease (78.0%) compared with non-Caucasian patients (71.4%), and patients with high-risk disease were managed similarly between groups. However, Caucasian patients with low-risk disease received more phlebotomies (56.6%) than non-Caucasian patients with low-risk disease (40.4%), and over twice as many non-Caucasian patients received hydroxyurea (38.6%) than Caucasian patients (15.6%) (Figure 1B). MPN-SAF TSSs were higher for non-Caucasian patients compared with Caucasian patients, suggesting a worse symptom burden. Similarly, non-Caucasian patients reported lower functional and symptom outcomes on the EORTC QLQ-C30, including a disparity in financial difficulties, compared to Caucasian patients (Figure 1C). Conclusions: This analysis evaluated a cohort of racial/ethnic minority patients with PV treated in the United States. As in other cancer-related trials, there is a risk that racial and ethnic minorities may be underrepresented in REVEAL. With this limitation in mind, in this analysis, differences were not observed among Caucasian and non-Caucasian patients with respect to method of diagnosis, duration of disease, thrombosis rates, or management of high-risk disease. Non-Caucasian patients demonstrated higher rates of low-risk disease and cytoreductive therapy for low-risk disease yet had worse symptom burden, lower functional scores, and greater disability. This study underscores the importance of symptom assessment and ancillary resource availability for patients with PV Disclosures Altomare: Bayer: Consultancy; Genentech: Consultancy; Ipsen: Other: Advisory Board Member; Celgene: Other: Advisory Board Member; Incyte: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership.

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