PD-1 Inhibitor and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer
Status:
Recruiting
Trial end date:
2024-09-21
Target enrollment:
Participant gender:
Summary
Overall survival (OS) of patients with advanced (stage IIIB/IV) non-small-cell lung cancer
(NSCLC) remains short after the first line of treatment with a median OS of 12.2 months in
non squamous NSCLC and 9.2 months in squamous NSCLC . In this setting the programmed death
1/ligand 1 (PD-1/-L1) were targeted with nivolumab (IgG4) in advanced squamous and
nonsquamous NSCLC leading to an increase of the 1-year OS rate of approximately 10-15% in
both histologies. Nivolumab, pembrolizumab and atezolizumab are now considered a standard of
care in 2nd line advanced NSCLC and in 1st line for pembrolizumab but but prognosis still
remains poor in advanced NSCLC. Overall survival (OS) of patients with advanced (stage
III/IV) NSCLC remains limited with a median OS of 12.2 months in non-squamous NSCLC and 9.2
months in squamous NSCLC if anti-PD1 alone. It is of around 16 months if pembrolizumab is
combined with chemotherapy.
Preclinical data indicates that anti-tumor efficacy is increased when anti-PD-1/-L1 are
combined with irradiation (IR). Radiotherapy alone can elicit tumor cell death which can
increase tumor antigen in the blood stream, favoring recognition by the immune system and its
activation against tumor cells outside of the radiation field (="abscopal effect").
IR may also reverse acquired resistance to PD-1 blockade immunotherapy by limiting T-cell
exhaustion.
Because of these preclinical and clinical data several studies analysing the combination of
IR and anti-PD1 in NSCLC are ongoing. Among them, two studies are testing the administration
of IR and nivolumab in stage III NSCLC: the NCT02768558 phase III trial (RTOG), and the
NCT02434081 phase II trial (ETOP). Antonia et al [2017] tested the use of anti-PD-L1 after
chemoradiotherapy in unresectable stage III NSCLC. Median time to distant metastasis was
increased (23.2 months vs. 14.6 months, p<0.001). An increase of OS is consequently expected.
However, no study involving concurrent RT and pembrolizumab combined with chemotherapy in
advanced NSCLC is ongoing, which is the purpose of the present study, NIRVANA-Lung.