How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review

Abstract

Patients with oligometastatic disease (OMD) non-small cell lung cancer (NSCLC) are considered as a subgroup of metastatic NSCLC that can obtain long-term survival or even cure. Oligometastatic refers to a state of a limited number of metastases in a limited number of organs. In clinical guidelines it is stated that patients with oligometastatic NSCLC can benefit from the addition of local radical therapy (LRT) to systemic therapy. With the introduction of minimally invasive surgery, advances in interventional radiology and stereotactic radiotherapy (SRT), LRT is becoming feasible for more and more patients. Furthermore, the introduction of immune checkpoint inhibitors (ICI) in the treatment landscape of advanced NSCLC has improved the survival of these patients. Importantly, the use of ICI in combination with LRT is also of interest in the subgroup of NSCLC patients with OMD. For example, it has been suggested that SRT may synergize with ICI as several preclinical studies reported an increased tumor antigen release, improved antigen presentation, and T-cell infiltration in irradiated tumors. In this narrative review, we describe the current evidence of immunotherapy treatment in OMD NSCLC, with a focus on future trial design and problems that need to be addressed.

Association between clinical outcomes and local treatment in stage IV non‐small cell lung cancer patients with single extrathoracic metastasis

“…Other studies also proved that local therapy to metastatic sites were associated with OS and PFS in oligometastatic patients 19–22 . Several prospective studies that evaluated efficacy of local ablative therapy and systemic treatment in oligometastatic NSCLC are reported 32–34 . NCT 01282450 enrolled 40 pathologically proven NSCLC stage IV patients with less than five metastases at initial diagnosis, and median PFS was 12.1 months 33 .…”

“…[19][20][21][22] Several prospective studies that evaluated efficacy of local ablative therapy and systemic treatment in oligometastatic NSCLC are reported. [32][33][34] NCT 01282450 enrolled 40 pathologically proven NSCLC stage IV patients with less than five metastases at initial diagnosis, and median PFS was 12.1 months. 33 The SINDAS study (NCT02893332), a phase III randomized control trial, evaluated the efficacy of upfront concurrent first generation tyrosine kinase inhibitors (TKI) with the addition of stereotactic ablative radiotherapy (SABR) versus without SABR in synchronous oligometastatic NSCLC with EGFR mutation.…”

Stereotactic body radiotherapy for extra-cranial oligoprogressive or oligorecurrent small-cell lung cancer

“…Another primary lung cancer occurrence may also exist, but most often after years of follow-up. It should also be highlighted that immunotherapy was not widely adopted at the time of our analysis or earlier reports [11] and that further synergistic effects with SBRT could hopefully happen [18] , [19] .…”

European Respiratory Society International Congress 2021: highlights from best-abstract awardees

“…Within the "State of the art: thoracic oncology" session, approaches to oligometastatic nonsmall cell lung cancer (NSCLC) were explored, including current guidelines advocating consideration of local consolidative therapy in addition to systemic treatment [47] and the potential roles of immunotherapy [48] and salvage surgical resection [49], given that this group may experience extended progression-free survival. During the "New clinical and biological developments in lung cancer" oral presentation session, J. Ramos Paradas (Spain) presented a research study conducted on a retrospective cohort of 196 individuals with NSCLC and described the novel immunophenotypes and potential biomarkers identified by the research group that may predict response to immunotherapy [50].…”