Trends in Phase II Trials for Cancer Therapies

Azam, F.; Vázquez, Alexei

doi:10.3390/cancers13020178

Cited by 8 publications

(4 citation statements)

References 63 publications

(39 reference statements)

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“…AEs, adverse events; CI, confidence interval chances of responding from targeted therapies were lower than from the combination of targeted therapies with chemotherapy. This observation is consistent with the previous findings showing the increased overall response rates in trials testing a combination of targeted therapies with cytotoxic drugs [32]. Unfortunately, a comparison of the overall benefits and risks in our meta-analysis to other studies is limited as the included sub-trials/arms were very heterogeneous, e.g., they were of different phases, and included heterogeneous populations and various types of cancers.…”

Section: Discussionsupporting

confidence: 90%

“…The safety and toxicity rates of anticancer agents in standard phase I-III clinical trials have already been estimated [26][27][28]. The recent analyses were focused on targeted therapies [29,30] which play an important role in precision medicine [31]; the performance of targeted therapies is enhanced when used in combination with cytotoxic drugs [32]. However, the only RCT in precision oncology was negative for survival [33].…”

Section: Introductionmentioning

confidence: 99%

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Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

Strzebońska

Blukacz

Wasylewski

et al. 2022

BMC Med

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Background Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy. Methods Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed. Results Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5–25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9–2.9), and the median OS was 7.1 months (95% CI 6.1–8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3–1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40–0.50). Conclusions Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

Strzebońska

Blukacz

Wasylewski

et al. 2022

BMC Med

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“…We did not compare the response rates between singledrug and multiple-drug studies because the majority of trials in our sample were single-drug studies. Previous studies have shown that using a combination of a few agents increases the likelihood of benefiting in a trial [17,39,40].…”

Section: Discussionmentioning

confidence: 99%

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

et al. 2021

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Background For research with human participants to be ethical, risk must be in a favorable balance with potential benefits. Little is known about the risk/benefit ratio for pediatric cancer phase II trials testing targeted therapies. Objective Our aim was to conduct a systematic review of preliminary efficacy and safety profiles of phase II targeted therapy clinical trials in pediatric oncology. Methods Our protocol was prospectively registered in PROSPERO (CRD42020146491). We searched EMBASE and Pub-Med for phase II pediatric cancer trials testing targeted agents. We included solid and hematological malignancy studies published between 1 January, 2015 and 27 February, 2020. We measured risk using drug-related grade 3 or higher adverse events, and benefit by response rates. When possible, data were meta-analyzed. All statistical tests were two-sided. Results We identified 34 clinical trials (1202 patients) that met our eligibility criteria. The pooled overall response rate was 24.4% (95% confidence interval [CI] 14.5-34.2) and was lower in solid tumors, 6.4% (95% CI 3.2-9.6), compared with hematological malignancies, 55.1% (95% CI 35.9-74.3); p < 0.001. The overall fatal drug-related (grade 5) adverse event rate was 1.6% (95% CI 0.6-2.5), and the average drug-related grade 3/4 adverse event rate per person was 0.66 (95% CI 0.55-0.78). Conclusions We provide an estimate for the risks and benefits of participation in pediatric phase II cancer trials. These data may be used as an empirical basis for informed communication about benefits and burdens in pediatric oncology research.

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“…Its main advantage is the ability to estimate e cacy early in-trial, allowing to leverage the results of Phase II trial for the "Go/No-Go" decision [13]. This endpoint showed no predictive capacity for some modern therapies [14,15] and, in some cases, a complementary endpoint, Disease Control Rate, was suggested, which reports the proportion of control (CR/PR/SD) vs. progression (PD), at the same timepoints. Another endpoint, Best Response, de ned as the best RECIST evaluation over a xed time period, or during the entire treatment course, is also used to summarize treatment e cacy, and was shown to be related to OS [16].…”

Section: Introductionmentioning

confidence: 99%

Absolute increase in tumour size can improve the metric evaluating disease progression in metastatic colorectal cancer

Robinson,

Agur,

Kogan

2024

Preprint

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Background The assessment of response to therapy in advanced solid cancer diseases is predicated on the Response Evaluation Criteria In Solid Tumours for the evaluation of disease state by the relative changes in lesion size. The underlying assumption is that a larger relative increase in lesion size implicates less efficacious therapy, worse prognosis and shorter survival. Methods We analyzed retrospective data of metastatic colorectal cancer patients from three clinical datasets, stratified into three cohorts by the treatment protocol. We evaluated the first relative and absolute increase in target lesion size for their association with overall survival. Results About fifty four percent of the patient population increased in target lesion size during the first-line treatment. A multivariate analysis showed that patients with larger relative increase in lesion size had slightly longer survival in all three cohorts (\(HR = 0.85, HR=0.95 ,HR = 0.75\) for Cohorts 1–3, respectively); p-values showed no significance. In contrast, patients with larger absolute increase in total lesion size had significantly shorter survival (\(HR = 1.1 \left(p=0.05\right), HR=1.2 \left(p=0.04\right), HR = 1.25(p=0.02)\) for Cohorts 1–3, respectively). We also found a negative correlation between the SLD at nadir and relative increase. Conclusions The different impact of the absolute and the relative increase in SLD at relapse reflects the different growth patterns of small and big tumours. Further validation of our results is required. We believe that the first absolute increase in total lesion size may become a useful metric, upon which a more precise categorization of survival-related disease progression can be based.

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Trends in Phase II Trials for Cancer Therapies

Cited by 8 publications

References 63 publications

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

Risk and benefit for umbrella trials in oncology: a systematic review and meta-analysis

Risk and Benefit for Targeted Therapy Agents in Pediatric Phase II Trials in Oncology: A Systematic Review with a Meta-Analysis

Absolute increase in tumour size can improve the metric evaluating disease progression in metastatic colorectal cancer

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