Inequality factors in access to early-phase clinical trials in oncology in France: results of the EGALICAN-2 study.

BACKGROUND: Investigation of the disparities in the access to experimental treatment in early-phase clinical trials is lacking. The objective of the EGALICAN-2 study was to identify the factors underpinning such inequalities. METHODS: A national prospective survey was conducted in 11 early-phase clinical trial centers (CLIP2) certified by the French National Cancer Institute. Sociodemographic, socioeconomic and medical data were collected. Univariate logistic regression models were carried out to estimate odds ratios and 90% confidence intervals associated with the effect of each study variable. A multivariate logistic regression model was built to explore the independent factors associated with the administration of the experimental treatment (C1D1). A post hoc analysis was carried out excluding female cancer patients. RESULTS: Between 2015 and 2016, 1355 patients referred from 11 CLIP2 centers in France were included in the study. Eight hundred and forty-eight patients received C1D1 (73%) and 320 patients (27%) were screening failure. Median age was 58 years (range 17-97 years) and 667 patients (54%) were female. Most patients had a metastatic disease (n = 751, 87%). In the multivariate logistic regression analysis, the significant independent factors associated with C1D1 were male sex, initial care received in a hospital with an early-phase unit and living in wealthy metropolitan areas (P values <0.05). In the post hoc analysis, the sex factor was no longer significant [odds ratio = 1.21 (95% confidence interval 0.86-1.70), P value = 0.271]. CONCLUSIONS: This study investigated the factors producing social inequalities in the context of early-phase clinical trials in oncology. Our research highlights factors of sex, care pathway and geographic location. Gynecological cancer was found to impact C1D1 significantly, unlike breast cancer. The results of this study should contribute to improve patient access to early-phase clinical trials.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

Access to early-phase clinical trials in older patients with cancer in France: the EGALICAN-2 study.

BACKGROUND: Access to clinical trials and especially early-phase trials (ECT) is an important issue in geriatric oncology. As cancer can be considered an age-related disease because the incidence of most cancers increases with age, new drugs should also be evaluated in older patients to assess their safety and efficacy. The EGALICAN-2 study was primarily designed to identify social and/or regional inequalities regarding access to ECT. We focused on the factors of inequalities in access to ECT in older patients. PATIENTS AND METHODS: During a 1-year period (2015-2016), a survey was conducted in 11 early-phase units certified by the French National Cancer Institute. RESULTS: A total of 1319 patients were included in the analyses: 1086 patients (82.3%) were <70 years and 233 patients (17.7%) were >70 years. The most common tumor types at referral in older patients were gastrointestinal (19.3%), hematological (19.3%), and thoracic tumors (18.0%). Most patients referred to the phase I unit had signed informed consent and the rate was similar across age (92.7% in younger patients versus 90.6% in older patients; P = 0.266). The rate of screening failure was also similar across age (28.5% in younger patients versus 24.3% in older patients; P = 0.219). Finally, in older patients, univariate analyses showed that initial care received in the hospital having a phase I unit was statistically associated with first study drug administration (odds ratio 0.49, 90% confidence interval 0.27-0.88; P = 0.045). CONCLUSIONS: Older patients are underrepresented in early clinical trials with 17.7% of patients aged ≥70 years compared with the number of new cases of cancer in France (50%). However, when invited to participate, older patients were prone to sign informed consent.

Impact of the timing of tumor assessments on median progression-free survival in clinical trials in advanced cancer patients.

BACKGROUND: Survival-based surrogate endpoints such as progression-free survival (PFS) are commonly used in oncology clinical trials. The evaluation-time bias in the assessment of median disease progression in randomized trials has been suggested by several simulation studies, but never demonstrated in the clinic. We aimed to demonstrate the existence of potential evaluation-time bias by assessing the impact of the timing of tumor assessments on median PFS from control arms without any active treatment of randomized controlled trials involving advanced cancer patients. MATERIALS AND METHODS: A systematic literature search of English language publications from 1 January 2000 to 7 January 2021 was performed using MEDLINE (PubMed). Eligible trials for our meta-analysis included all randomized clinical trials evaluating anticancer drugs in adult patients with advanced cancers with a control arm without any anticancer drug consisting of best supportive care with or without a placebo. We performed a meta-regression analysis to analyze the correlation between the timing of the first tumor assessment and median PFS in patients randomized in the control arms without any active treatment. RESULTS: Of 3551 studies screened, 97 eligible trials were retrieved involving 36  747 patients, including 14  229 patients randomized into the control arms. A later first tumor assessment correlated with a prolonged median PFS (R2 = 0.44, P < 10-5). CONCLUSIONS: Our results confirm the existence of potential evaluation-time bias in clinical research that had been suggested by simulation studies. The timing of tumor assessments should be kept the same in precision medicine trials using the PFS ratio as an efficacy endpoint.

Patients' perceived tolerance of side effects in phase I cancer clinical trials: A qualitative study.

This qualitative study aimed to explore cancer patients' perceived tolerance of side effects in phase I drug trials. Patients with solid tumours receiving molecularly targeted agents with/without chemotherapy were eligible for inclusion. In-depth semi-structured interviews were carried out with 17 patients with a median [range] age of 63 [41-72] years. Treatment was discontinued in seven patients. Verbatim transcripts of the audio-taped interviews were analysed using a constructivist grounded theory approach. Four conceptual categories emerged from data analysis, labelled "suffering from side effects" comprising a range of symptoms, psychosocial or role disturbances; "striving to cope with side effects" reflecting psychological strategies for managing side effects; "hoping" reflecting expectations about treatment efficacy and relief from side effects; and "appraisal of care." Among patients remaining in the trial, treatment was currently perceived as fairly tolerable. For most respondents, whether still in a trial or not, treatment discontinuation could not be justified by the non-tolerance of treatment side effects. These results question the adequacy of patient-perceived tolerance reports to determine an optimal drug dose for phase II trials. Confronted with patients' hopes and inappropriate beliefs, communication is challenging in phase I trials and could benefit from facilitating psychosocial interventions.