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How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials.

ABSTRACT: Background:In 2012, 11 standards describing best supportive care (bsc) in clinical trials in advanced cancer were defined through consensus statements. The consensus included 15 key components. Our objective was to analyze whether clinical trials that involved patients with advanced cancer and that included bsc in at least 1 arm met the standards and contained the key components. Methods:We reviewed clinical trials registered in ClinicalTrials.gov, the isrctn (International Standard Randomised Controlled Trial Number) registry, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform for 2012-2018. We selected only phase iii studies in patients with advanced cancer that included bsc in at least 1 arm. We describe the characteristics of the trials, together with the definition and components of bsc. We analyzed how the trials met the standards and adopted the key components of bsc. Results:Of 193 trials retrieved, only 64 met the inclusion criteria; 36 of those trials (56%) had no definition of bsc. Less than 7% of the trials included even 3 of the 8 bsc standards that were defined to be included in the design of trials. Furthermore, trials mentioned only 5 of the 15 key components that the consensus defined to be fundamental, with symptom management appearing in 22% of trials and the other 4 components appearing in less than 8%. Summary:Most clinical trials registered during 2012-2018 that involved patients with cancer and an arm with bsc did not define the bsc concept. Hence, the design of those trials does not meet the consensus recommendations.

SUBMITTER: Sanz Rubiales A

PROVIDER: S-EPMC7253756 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials.

Sanz Rubiales Á Á Sánchez-Gutiérrez M E ME Flores Pérez L A LA Del Valle Rivero M L ML

Current oncology (Toronto, Ont.) 20200401 2

<h4>Background</h4>In 2012, 11 standards describing best supportive care (bsc) in clinical trials in advanced cancer were defined through consensus statements. The consensus included 15 key components. Our objective was to analyze whether clinical trials that involved patients with advanced cancer and that included bsc in at least 1 arm met the standards and contained the key components.<h4>Methods</h4>We reviewed clinical trials registered in ClinicalTrials.gov, the isrctn (International Standa ...[more]

PMID: 32489259

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Project description:ImportanceSingle-agent immune checkpoint inhibition has not shown activities in advanced refractory colorectal cancer (CRC), other than in those patients who are microsatellite-instability high (MSI-H).ObjectiveTo evaluate whether combining programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition improved patient survival in metastatic refractory CRC.Design, setting, and participantsA randomized phase 2 study was conducted in 27 cancer centers across Canada between August 2016 and June 2017, and data were analyzed on October 18, 2018. Eligible patients had histologically confirmed adenocarcinoma of the colon or rectum; received all available standard systemic therapies (fluoropyrimidines, oxaliplatin, irinotecan, and bevacizumab if appropriate; cetuximab or panitumumab if RAS wild-type tumors; regorafenib if available); were aged 18 years or older; had adequate organ function; had Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease.InterventionsWe randomly assigned patients to receive either 75 mg of tremelimumab every 28 days for the first 4 cycles plus 1500 mg durvalumab every 28 days, or best supportive care alone (BSC) in a 2:1 ratio.Main outcomes and measuresThe primary end point was overall survival (OS) and a 2-sided P<.10 was considered statistically significant. Circulating cell-free DNA from baseline plasma was used to determine microsatellite instability (MSI) and tumor mutation burden (TMB).ResultsOf 180 patients enrolled (121 men [67.2%] and 59 women [32.8%]; median [range] age, 65 [36-87] years), 179 were treated. With a median follow-up of 15.2 months, the median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for BSC (hazard ratio [HR], 0.72; 90% CI, 0.54-0.97; P = .07). Progression-free survival was 1.8 months and 1.9 months respectively (HR, 1.01; 90% CI, 0.76-1.34). Grade 3 or 4 adverse events were significantly more frequent with immunotherapy (75 [64%] patients in the treatment group had at least 1 grade 3 or higher adverse event vs 12 [20%] in the BSC group). Circulating cell-free DNA analysis was successful in 168 of 169 patients with available samples. In patients who were microsatellite stable (MSS), OS was significantly improved with durvalumab and tremelimumab (HR, 0.66; 90% CI, 0.49-0.89; P = .02). Patients who were MSS with plasma TMB of 28 variants per megabase or more (21% of MSS patients) had the greatest OS benefit (HR, 0.34; 90% CI, 0.18-0.63; P = .004).Conclusions and relevanceThis phase 2 study suggests that combined immune checkpoint inhibition with durvalumab plus tremelimumab may be associated with prolonged OS in patients with advanced refractory CRC. Elevated plasma TMB may select patients most likely to benefit from durvalumab and tremelimumab. Further confirmation studies are warranted.Trial registrationClinicalTrials.gov Identifier: NCT02870920.

Project description:Maintenance therapy for non-small cell lung cancer (NSCLC) aims to extend disease control after first-line chemotherapy with active and well-tolerated agents. The utility of continuation maintenance therapy requires further research.This multicenter, randomized, phase 2 study compared continuation maintenance therapy with pemetrexed (500?mg/m2 every 21?days) and best supportive care (BSC) versus BSC alone in patients with advanced, non-squamous NSCLC who had not progressed after 4?cycles of induction chemotherapy with pemetrexed (500?mg/m2) and cisplatin (75?mg/m2). The primary endpoint was progression-free survival (PFS) from randomization, was analyzed using a Cox model, stratified for the tumor response at the end of induction therapy, at a one-sided alpha of 0.2. Secondary endpoints: response and disease control rates, overall survival (OS), one year survival rates, and treatment-emergent adverse events (TEAEs).A total of 106 patients commenced induction therapy, of whom 55 patients were randomized to maintenance pemetrexed/BSC (n?=?28) or BSC (n?=?27). Although the median PFS time for maintenance phase for both arms was 3.2?months, the one-sided p-value for the PFS HR comparison was less than the prespecified limit of 0.2 (HR?=?0.76, two-sided 95% confidence interval [CI]: 0.42 to 1.37; one-sided p-value?=?0.1815), indicating that PFS was sufficiently long in the pemetrexed/BSC arm to warrant further investigation. Similar PFS results were observed for the overall study period (induction plus maintenance) and when the PFS analysis was adjusted for sex, baseline disease stage, and the ECOG PS prior to randomization. The median OS for the maintenance phase was 12.2?months (95%CI: 5.6 to 20.6) for the pemetrexed/BSC arm and 11.8?months (95% CI: 6.3 to 25.6) for BSC arm. The one-year survival probabilities were similar for both arms for the maintenance phase and the overall study period. Both the induction and continuation maintenance therapies were generally well-tolerated, and similar proportion of patients in each arm experienced at least 1 grade 3/4 TEAE (pemetrexed/BSC, 17.9%; BSC, 18.5%).Continuation pemetrexed maintenance therapy resulted in promising PFS with an acceptable safety profile in a Middle Eastern population with advanced non-squamous NSCLC and is worthy of further investigation.NCT00606021.

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How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials.

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How is best supportive care provided in clinical trials for patients with advanced cancer? A review of registered protocols of clinical trials.

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