TY - JOUR
T1 - Maximizing Treatment Opportunities
T2 - Assessing Protocol Waivers’ Impact on Safety and Outcome in the Drug Rediscovery Protocol
AU - van Berge Henegouwen, Jade M.
AU - Zeverijn, Laurien J.
AU - Geurts, Birgit S.
AU - Hoes, Louisa R.
AU - van der Wijngaart, Hanneke
AU - van der Noort, Vincent
AU - Huitema, Alwin D.R.
AU - de Vos, Filip Y.F.
AU - Grünberg, Katrien
AU - Bloemendal, Haiko J.
AU - Verheul, Henk M.W.
AU - Voest, Emile E.
AU - Gelderblom, Hans
N1 - Publisher Copyright:
©2024 American Association for Cancer Research.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - Purpose: Although eligibility criteria are essential in trial design, overly restrictive criteria contribute to low accrual and limited generalizability. To enhance trial inclusivity, there has been growing interest in broadening eligibility criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In the Drug Rediscovery Protocol (DRUP), protocol exceptions are frequently requested and occasionally granted. Here we describe the impact of these waivers on treatment safety and efficacy.Experimental Design: DRUP is a multicenter, nonrandomized clinical basket trial treating patients with therapy-refractory cancer with molecularly targeted and immunotherapies outside their registered indications (NCT02925234). Here, all granted waivers were revised, analyzed in terms of safety and efficacy outcome, and com-paredwithoutcomes of includedpatientswho didnot receive awaiver. Results: Between September 1, 2016, and September 1, 2021, protocol waivers were granted for 82 patients (8%) of 1,019 included patients in DRUP. Most waivers (45%) were granted for general- or drug-related eligibility criteria; other categories were out-of-window testing, treatment, and testing exceptions. Serious adverse event rate was similar between patients who received a waiver (pW) and patients who did not (pNW): 39% vs. 41%, respectively (P ¼ 0.81). The clinical benefit (either objective response or stable disease ≥ 16 weeks) rate of pW was 40% versus 33% in pNW (P ¼ 0.43). Conclusions: Safety and clinical benefit were preserved in patients for whom a waiver was granted. These data support a more personalized approach in assessing eligibility criteria, especially in trials with widely used and approved drugs accruing patients without other treatment options.
AB - Purpose: Although eligibility criteria are essential in trial design, overly restrictive criteria contribute to low accrual and limited generalizability. To enhance trial inclusivity, there has been growing interest in broadening eligibility criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In the Drug Rediscovery Protocol (DRUP), protocol exceptions are frequently requested and occasionally granted. Here we describe the impact of these waivers on treatment safety and efficacy.Experimental Design: DRUP is a multicenter, nonrandomized clinical basket trial treating patients with therapy-refractory cancer with molecularly targeted and immunotherapies outside their registered indications (NCT02925234). Here, all granted waivers were revised, analyzed in terms of safety and efficacy outcome, and com-paredwithoutcomes of includedpatientswho didnot receive awaiver. Results: Between September 1, 2016, and September 1, 2021, protocol waivers were granted for 82 patients (8%) of 1,019 included patients in DRUP. Most waivers (45%) were granted for general- or drug-related eligibility criteria; other categories were out-of-window testing, treatment, and testing exceptions. Serious adverse event rate was similar between patients who received a waiver (pW) and patients who did not (pNW): 39% vs. 41%, respectively (P ¼ 0.81). The clinical benefit (either objective response or stable disease ≥ 16 weeks) rate of pW was 40% versus 33% in pNW (P ¼ 0.43). Conclusions: Safety and clinical benefit were preserved in patients for whom a waiver was granted. These data support a more personalized approach in assessing eligibility criteria, especially in trials with widely used and approved drugs accruing patients without other treatment options.
UR - http://www.scopus.com/inward/record.url?scp=85203204691&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-3917
DO - 10.1158/1078-0432.CCR-23-3917
M3 - Article
C2 - 38926908
AN - SCOPUS:85203204691
SN - 1078-0432
VL - 30
SP - 3937
EP - 3943
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -