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The standard first-line treatment for non-oncogene driven metastatic non-small cell lung cancer (NSCLC) is an immune checkpoint inhibitor (ICI) based strategy. Although guidelines increasingly advise adding local radical treatment (LRT) to patients with synchronous oligometastatic (sOMD) NSCLC responding to systemic therapy, this recommendation is based on the studies without ICI. Furthermore, the majority of published oligometastatic studies were not on an intention-to-treat basis, resulting in selection bias. Moreover, staging Positron Emission Tomography-Computed Tomography (PET-CT) and brain imaging were often not mandatory and definitions of oligometastatic were heterogeneous. Therefore, this study focused on a single centre retrospective series, including all adequately staged patients with sOMD NSCLC according to the European Organisation for Research and Treatment of Cancer definition (maximum of 5 metastases in 3 organs) that were treated with induction (chemo)-ICI and compared outcomes to those treated with chemotherapy only, with and without LRT. The primary end-points were median progression-free survival (PFS) and overall survival (OS) for patients treated with induction (chemo)-ICI versus chemotherapy. Out of 68 included patients, 38 (56%) eventually received LRT. With a median follow-up of 26.7 months, the median PFS was 19.0 months for (chemo)-ICI (n = 18) versus 6.8 for chemotherapy-only (n = 50) (HR 0.5, p = 0.03), the median OS was 19.3 versus 15.7 months, respectively (HR 0.8, p = 0.4). In patients having received LRT, median PFS was 19.0 months for (chemo)-ICI versus 8.3 for chemotherapy-only (HR 0.6, p = 0.2). In conclusion, an ICI-based systemic treatment is feasible and may result in superior survival outcomes. This should be investigated in prospective trials. Strategies to improve response rates to systemic treatment are also needed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LH: Outside of this manuscript personal fees as an invited speaker from Benecke, Medtalks, Medimix and VJOncology; personal fees for participation in mentorship programme funded by AstraZeneca; personal fees for travel support from Roche; personal fees as member of the committee that revised the Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases; fees paid to her institution for an educational webinar from Janssen; fees paid to her institution for advisory board membership from Amgen, BMS, Boehringer Ingelheim, Janssen, Lilly, Merck, MSD, Novartis, Pfizer, Roche and Takeda; fees paid to her institution as an invited speaker from AstraZeneca, Bayer, high5oncology, Lilly and Merck Sharp & Dohme (MSD); fees paid to her institution for interview sessions from Roche; fees paid to her institution for podcast appearance from Takeda; institutional research grants from AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Merck and Pfizer (Novartis under negotiation); institutional funding as a local principal investigator (PI) from AbbVie, AstraZeneca, Blueprint Medicines, Gilead, GlaxoSmithKline (GSK), Merck Serono, Mirati, MSD, Novartis, Roche and Takeda; non-remunerated roles as chair for metastatic NSCLC of the lung cancer group for EORTC (European Organisation for Research and Treatment of Cancer) and as the secretary of the studies foundation for NVALT (Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose). DR: Outside of this manuscript research grant/ support/ Advisory Board: Institutional financial interests (no personal financial interests) from AstraZeneca, BMS, Beigene, Philips, Olink and Advisory Board: Institutional financial interests (no personal financial interests) for Eli-Lilly. MJ,VB,TL,MS,SD: None declared., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Adjuvant durvalumab is the standard of care for patients with stage III unresectable non-small cell lung cancer (NSCLC), without progression after concurrent chemo-radiation (CCRT). Patients with stage III NSCLC harbouring epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements do not seem to benefit from durvalumab. Data are lacking about patients harbouring other driver genomic alterations (dGA). We performed a multicentre (N = 4, Netherlands and Italy) retrospective study including consecutive patients with unresectable stage III NSCLC and treated with CCRT-with or without adjuvant durvalumab-between 2016 and 2022. We enrolled 271 patients; 130 of which received adjuvant durvalumab. Sixty-six patients had dGA (41 KRAS mutations, 4 EGFR common mutations and 21 uncommon dGA). In the entire population, the median PFS was 24.9 months (95% CI 17.5-32.4) and 12.6 months (95% CI 9.0-16.1) with and without durvalumab (p = 0.001). In the dGA group (excluding common EGFR), mPFS was 12.3 months (95% CI 7.8-16.8) with and 7.6 (95% CI 3.4-11.9) without durvalumab (p = 0.038). For patients with KRAS mutations, mPFS was 12.3 months (95% CI 3.6-20.9) with and 7.2 months (95% CI 1.8-12.6) without durvalumab (p = 0.12). Among patients with uncommon dGA, mPFS was 12.9 months (95% CI 8.4-17.4) with and 7.6 months (95% CI 1.4-14) without durvalumab (p = 0.23). We have shown a meaningful survival benefit of adjuvant durvalumab in patients harbouring KRAS mutations and uncommon dGA. This is the largest stage III NSCLC cohort showing the efficacy of durvalumab in patients with uncommon dGA. Further prospective studies are needed to confirm our results., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC: Lilly, Travel expenses, Institutional; AstraZeneca, Local PI, Institutional. DDR: AstraZeneca, Research Grant, Institutional; AstraZeneca, Steering Committee Member, Institutional, AstraZeneca, Coordinating PI, Institutional, BeiGene, Funding, Institutional, BMS, Research Grant, Institutional, BMS, Coordinating PI, Institutional, Olink, Funding, No financial interest. Philips Health, Steering Committee Member, Institutional, Varian, Research Grant, Institutional. MS: No conflict of interest to declare. RW: No conflict of interest to declare. AvdW: Received research grants from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche and Takeda outside the current work. Was involved in advisory boards of AstraZeneca, Janssen, Lilly, Roche and Takeda and was speaker in educational meetings sponsored by AstraZeneca, BMS, Lilly, Pfizer and Roche. Involved in clinical studies for AstraZeneca, Amgen, Blueprint medicine, Nuvalent, Novartis, Merck, Pfizer, Roche and Takeda. Payments from Dutch Guidelines for NSCLC. All finances received by the UMCG. Non-financial: Board Member Dutch Oncology Group (NVALT), Member of Patient Panel of Longkanker Nederland and Member of Patient Advisory Panel of ROS1ders. MA: No conflict of interest to declare. LH: Amgen, Advisory Board, Institutional; AstraZeneca, Other, Personal, Mentorship with key opinion leaders funded by AstraZeneca; AstraZeneca, Invited Speaker, Institutional for educational webinar; Bayer, Invited Speaker, Institutional; Educational webinar/interview, Benecke, Invited Speaker, Personal, payment for post ASCO/ESMO/WCLC presentations, educational committee member; BMS, Advisory Board, Institutional; Boehringer Ingelheim, Advisory Board, Institutional; high5oncology, Invited Speaker, Institutional, payment for post ESMO/ASCO discussion; Janssen, Advisory Board, Institutional; Janssen, Other, Institutional, Educational webinar. Lilly, Advisory Board, Institutional; Lilly, Invited Speaker, Institutional, for educational webinar; Medtalks, Invited Speaker, Personal, for webinars; Merck, Advisory Board, Institutional; MSD, Advisory Board, Institutional; MSD, Invited Speaker, Institutional, educationals; Novartis, Advisory Board, Institutional; Pfizer, Advisory Board, Institutional; Roche, Other, Personal, travel support; Roche, Other, Institutional, performing interviews at conference; Roche, Advisory Board, Institutional, one time also personal; Takeda, Advisory Board, Institutional. Takeda, Other, Institutional, podcast on brain metastases; VJOncology, Invited Speaker, Personal, payment for post ASCO round table discussion; Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases, Other, Personal, member of the committee that revised these guidelines; Abbvie, Local PI, Institutional; AstraZeneca, Local PI, Institutional; AstraZeneca, Research Grant, Institutional; Blueprint Medicines, Local PI, Institutional; Boehringer Ingelheim, Research Grant, Institutional; Gilead, Local PI, Institutional; GSK, Local PI, Institutional; Merck, Research Grant, Institutional, donation for health care improvement project; Merck Serono, Local PI, Institutional; Mirati, Local PI, Institutional, MSD, Local PI, Institutional; Novartis, Local PI, Institutional; Pfizer, Research Grant, Institutional, funding for healthcare improvement project; Roche, Local PI, Institutional; Roche, Research Grant, Institutional; Takeda, Local PI, Institutional, Research Grant, Institutional. Non-financial interests: EORTC, chair metastatic NSCLC for lung cancer group, NVALT, secretary NVALT studies foundation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)