2413 - Implementation of PRO-CTCAE in phase I clinical trials identifies under reporting of adverse events

Background

The goal of phase I trials is to determine adverse event (AE) profiles of new therapies. Typically, AEs are captured by clinicians, yet patient reported outcome (PRO) tools collect AEs which may be under reported. Our single center, prospective study aimed to validate PRO-CTCAE in phase I clinical trial patients (pts).

Methods

Pts eligible for phase I trials at Princess Margaret Cancer Centre were evaluated using tablet based, PRO-CTCAE with the full item library (n = 80) in addition to standard, matched clinician reported CTCAE grading of AEs at baseline (BL), mid cycle 1 (C1) and 2 (C2). Overall (BL + C1 + C2) totals were also assessed. Characteristics (age, gender, tumor group, ECOG, education), best response (using RECIST v1.1), and treatment information were collected. Comparative (kappa) statistics were used to assess agreement of patient and clinician reported AEs.

Results

Of 292 pts approached (05/2017 to 01/2019), 265 (91%) were consented and 243 (92%) were evaluable, with 552 surveys completed. Median age was 61 (range 18-82), 51% were female, and 79% were ECOG 1; with GI (31.7%), head and neck (13.2%), and breast (10.7%) as frequent tumor types. Pts were commonly treated with immune (66%) and/or targeted (21%), mono (35%) or combination (61%) therapy. PRO-CTCAE completion rates were high (98.7%), with fatigue (75%), pain (68%), and anxiety (54%) as often reported overall patient AEs. Common physician reported AEs were fatigue (41%), pain (39%) and insomnia (18%). Overall patient-clinician agreement (kappa), was poor for fatigue (0.12) and anxiety (0.08), and fair for pain (0.28). Clinician reported insomnia (0.2) was fair. Highest patient-clinician agreement was seen for dyspnea at BL (0.54), and edema (0.55) and rash (0.49) at C2. Despite patient reporting, clinicians did not report select AEs (palpitations, hiccups, vaginal dryness), and had poor overall agreement for cognitive (0-0.03), urinary (0.02-0.05), and mood (0.05-0.08) symptoms.

Conclusions

Completion of PRO-CTCAE was high in phase I trial pts. Clinician reported AEs had poor to fair agreement compared with PRO-CTCAE, suggesting under-reporting in phase I trials. This information could inform a phase I PRO survey to complement clinician reported AEs. Analyses are ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Drug Development Department, Princess Margaret Cancer Centre.

Funding

Has not received any funding.

Disclosure

A.A. Razak: Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (institution): CASI; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Amgen; Honoraria (self): Boehringer Ingelheim. A. Spreafico: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: Oncorus; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Janssen Oncology/Johnson & Johnson. P. Bedard: Research grant / Funding (institution): BMS; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Servier; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): SignalChem; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly; Research grant / Funding (self): Pfizer. L.L. Siu: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Loxo; Advisory / Consultancy: Oncorus; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy: Morphosys; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy: GeneSeeq; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Seattle Genetics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Intensity Therapeutics; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Mirati. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Karyopharm. All other authors have declared no conflicts of interest.