ABSTRACT
The coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care.
Subject(s)
COVID-19 , Neoplasms , Telemedicine , Clinical Trials as Topic , Humans , Neoplasms/epidemiology , Neoplasms/therapy , Pandemics , SARS-CoV-2ABSTRACT
Background: The long-term benefit of adjuvant dab + tram in pts with resected stage III BRAFV600E/K-mutant melanoma was demonstrated in COMBI-AD where AEs led to permanent discontinuation of dab + tram in 26% of pts, most often due to pyrexia (9%). The COMBIAPlus trial (NCT03551626) is designed to evaluate whether an adapted pyrexia management algorithm could reduce high-grade pyrexia and other pyrexia-related adverse outcomes, such as treatment cessation and hospitalization. Methods: COMBI-APlus is an open-label, Phase IIIb trial evaluating an adapted pyrexia management algorithm in pts with high-risk resected stage III BRAF V600E/K-mutant melanoma treated with 12 mo of adjuvant dab + tram. In the adapted algorithm, both dab and tram were interrupted promptly at the onset of pyrexia (temperature ≥ 38°C). In the event of suspected recurrent pyrexia, treatment may be interrupted in the presence of pyrexia syndrome (ie, chills, rigors, night sweats, or influenza-like symptoms without temperature ≥ 38°C) at investigator discretion. Treatment with dab + tram was restarted at the same dose level once pts were symptom free for ≥ 24 hours. The primary endpoint is the composite rate of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent discontinuation due to pyrexia vs a historical control from COMBI-AD (20%;95% CI, 16.3%-24.1%). Secondary endpoints include relapse-free survival (RFS) and safety. Results: A total of 552 pts were enrolled. At the data cutoff (5 Oct 2020), all pts had completed 12 mo of treatment;median duration of follow-up was 18.4 mo. COMBI-APlus met its primary endpoint of significant improvement in composite rate of pyrexia. The composite rate was 8.0% (95% CI, 5.9%-10.6%), with rates of 3.8% for grade 3/4 pyrexia, 4.3% for hospitalization due to pyrexia, and 2.4% for discontinuation due to pyrexia. The estimated 12-mo RFS rate was 91.8% (95% CI, 89.0%-93.9%). The most common AEs (≥ 20%) were pyrexia (67.8%), headache (31.7%), blood creatine phosphokinase increase (27.9%), diarrhoea (27.0%), chills (26.4%), fatigue (25.7%), asthenia (23.6%), nausea (23.4%), rash (21.4%), and arthralgia (21.0%). AEs of any type led to permanent dab + tram discontinuation in 14.7% of pts. Conclusions: This primary analysis suggests the new adapted pyrexia management algorithm is effective in reducing grade 3/4 pyrexia, pyrexiarelated hospitalization, and treatment discontinuation in pts receiving adjuvant dab + tram. The early efficacy appears consistent with that observed in COMBI-AD. The growing experience of oncologists in managing pyrexia with this simple algorithm may reduce the need for hospitalization or visits to a healthcare provider, which is highly desirable during the current COVID- 19 pandemic. Thus, more pts can remain on treatment and derive benefit.