Extended-Interval Dosing Strategy of Immune Checkpoint Inhibitors in Lung Cancer: Will it Outlast the COVID-19 Pandemic?

Abstract

Patients with lung cancer are particularly vulnerable to complications from coronavirus disease-2019 (COVID-19). Recurrent hospital visits and hospital admission are potential risk factors for acquiring infection with its causative pathogen, severe acute respiratory syndrome coronavirus−2 (SARS-CoV-2). As immune checkpoint inhibitors (ICIs) constitute the therapeutic backbone for the vast majority of patients with advanced lung cancer in the absence of actionable driver oncogenes, there have been intense discussions within the oncology community regarding risk-benefit of delaying these treatments or use of alternative extended-interval treatment strategies to minimize the risk of viral transmission secondary to unintended nosocomial exposures. In the midst of the COVID-19 pandemic, the U.S. Food and Drug Administration (FDA) granted accelerated approval for extended-interval strategy of pembrolizumab at a dose of 400 mg every 6 weeks for all already approved oncologic indications. Herein, we summarize the evidence from the in silico pharmacokinetic modeling/simulation studies supporting extended-interval dosing strategies for the ICIs used in lung cancer. We further review the evolving clinical evidence behind these approaches and predict that they will continue to be used in routine practice even long after the pandemic, particularly for patients with durable disease control.

Does immune checkpoint inhibitor increase the risks of poor outcomes in COVID-19-infected cancer patients? A systematic review and meta-analysis

“…This is especially important to ensure prompt diagnosis and treatment of COVID-19 infections, thus preventing adverse outcomes in such patients. The decision to continue or suspend ICI treatment should be based on case-by-case approaches [ 44 , 50 ], where treatment adjustments may be performed to mitigate the risk of COVID-19 infection by reducing patients’ contacts to medical system, rather than due to ICI-related safety concerns. This is saliently important considering that cancer patients receiving active anticancer therapy may be at an increased COVID-19 infection risk due to frequent visits to hospitals [ 51 ].…”

Clinical and immunologic implications of COVID-19 in patients with melanoma and renal cell carcinoma receiving immune checkpoint inhibitors

“… 30 95 104 We therefore agree with recently published consensus guidelines from the UK, 105 106 including continued use of front-line ICI therapies and to consider the approved alternative dosing regimens of either pembrolizumab 400 mg every 6 weeks as opposed to initial 3-week standard of care dosing per KEYNOTE-555 Cohort B data as well as nivolumab 480 mg every 4 weeks compared with every 2-week standard of care for those on nivolumab maintenance regimens. 107 …”

The Influence of Different Anti-PD-1 Monoclonal Antibody Concentrations On T Cell Activation in in - Vitro Culture – A Preliminary Study

“…Third phase clinical trials CheckMate-066, -025, -057, and -017 showed similar PFS times and frequencies of side effects of 480 mg/kg Q4 W nivolumab dose compared to the standard scheme in patients after disease progression. Additionally, preliminary data from CheckMate-384 in pretreated patients with advanced-stage IIIB/IV NSCLC showed no signi cant differences between subgroups treated with 480 mg/kg Q4 W vs. 240 mg/kg Q2 W. The recorded adverse effect percentage was similar, with data from patients treated with 3 mg/kg Q3 W 29 . The more frequent use of lower doses might be more convenient for patients during the pandemic, according to cited research.…”