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

Jordi Remon, Jessica Menis, Antonin Levy, Dirk K M De Ruysscher, Lizza E L Hendriks, Jordi Remon, Jessica Menis, Antonin Levy, Dirk K M De Ruysscher, Lizza E L Hendriks

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.

Keywords: Clinical trials; immunotherapy; local radical therapy; non-small cell lung cancer (NSCLC); oligometastatic; radiotherapy.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1065). The series “Oligometastatic NSCLC: definition and treatment opportunities” was commissioned by the editorial office without any funding or sponsorship. JR serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2019 to September 2021. AL serves as an unpaid editorial board member of Translational Lung Cancer Research from September 2019 to September 2021. JR reports other from OSE PHARMA, ASTRA ZENECA, MSD, PFIZER and ROCHE, outside the submitted work. JM reports grants, personal fees and other from Boehringer-Ingelheim, grants and other from MSD, Roche, Astrazeneca, Ipsen and BMS, outside the submitted work. DDR reports grants from Brsitol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Philips, Olink, Celgene, Seattle Genetics, Roche/Genentech and Merck/Pfizer, outside the submitted work. LH reports other from boehringer ingelheim, BMS, Roche Genentech and BMS, grants from Roche Genentech and Boehringer Ingelheim, other from AstraZeneca, personal fees from Quadia, grants from Astra Zeneca, other from Eli Lilly, Roche Genentech, Pfizer, MSD and Takeda, non-financial support from AstraZeneca, Novartis, BMS, MSD/Merck, GSK, Takeda, Blueprint Medicines and Roche Genentech, other from Amgen, outside the submitted work. The authors have no other conflicts of interest to declare.

2021 Translational Lung Cancer Research. All rights reserved.

Figures

Figure 1
Figure 1
Challenges in the design of immunotherapy trials for OMD NSCLC. OMD, oligometastatic disease; CR, complete response; MRD, minimal residual disease; ICI, immune checkpoint inhibitor; ctDNA, circulating tumor DNA; LRT, local radical therapy; SD, stable disease; RR, response rate; RT, radiotherapy.

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