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Objectives: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP)., Methods: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI)., Results: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients., Conclusions: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Aim: To define high tumor burden (HTB) in non-small-cell lung cancer. Methods: A total of five oncologists initiated the project, selecting 66 participants, and elaborated a questionnaire with 26 statements using the Delphi method with a 9-point Likert scale of agreement. Results: Factors with moderate strength of consensus were identified, including a sum of the longest diameter of lesions ≥10 cm, elevated Lactate dehydrogenase, hepatic involvement, lymphangitis carcinomatosis, brain involvement unapproachable with local techniques and pericardial effusion. There was a consensus against increases in tumor markers and asymptomatic brain involvement being related to HTB. HTB was considered a relevant factor for treatment selection supporting the choice of combination regimens versus immunotherapy only. Conclusion: In this Delphi study, experts defined several factors associated with HTB in non-small cell lung cancer.

In recent years, major advances have been achieved in our understanding of non-small-cell lung cancer (NSCLC) with oncogenic driver alterations and in the specific treatment of these with tyrosine kinase inhibitors. Currently, state-of-the-art management of patients with NSCLC (particularly adenocarcinoma or non-adenocarcinoma but with mild tobacco exposure) consists of the determination of EGFR , ALK , ROS1  and BRAF status, as they have US FDA and EMA approved targeted therapies. The increase in molecular knowledge of NSCLC and the development of drugs against other targets has settled new therapeutic indications. In this review we have incorporated the development around MET, KRAS and NTRK in the diagnosis of NSCLC given the therapeutic potential that they represent, as well as the drugs approved for these indications.

Introduction: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised., Material and Methods: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA., Results: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02)., Conclusions: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings., Competing Interests: Conflict of interest statement MMj: advisory and consultancy honoraria from Roche, Merck, BristolMyers Squibb, AstraZeneca, Amgen, Boehringer, Sanofi and Takeda; speaker honoraria from Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Bayer, Amgen, Pfizer and Boehringer; grants from AstraZeneca and BristolMyers Squib, and travel/accommodation expenses from Roche, Merck and Lilly. RLC: honoraria from Kyowa Kirin, Pierre-Fabre, Takeda, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Roche, Merck Serono, Pfizer; consulting or advisory role from Roche, Astra-Zeneca, Boehringer Ingelheim, Aristo, Novartis; research funding from Roche, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, AstraZeneca. JBB: grants and personal fees from Roche-Genentech, Pfizer, MSD, BMS, Astrazeneca, Novartis, Boehringer-Ingelheim, Vifor, Sanofi, LEO Pharma, outside the submitted work. SP: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Roche, Amgen. MT: travel grants from Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; honoraria as medical writer from Novartis, Amgen. GZ: research grants from Roche-France, Bristol-Myers Squibb, and Takeda outside of the submitted work; perceived fees from Bristol-Myers Squibb, AstraZeneca, Pfizer, and Boehringer Ingelheim outside the submitted work; and reimbursement for international meetings assistance from AbbVie, Merck Sharp & Dohme, AstraZeneca, Bristol-Myers Squibb, and Roche-France. XM-R: Research grant funding from Brystol-Myers Squibb; consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD; clinical trials research from Boehringer Ingelheim, Pfizer, Roche, Abbvie; travel, accommodations and expenses from Roche, Pfizer, Brysto-Myers Squibb. JB: educational grants by AMGEN. MSch: speaker and advisory role honoraria, travel accommodations from AMGEN, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Pfizer, Roche, Takeda; personal research support from AMGEN, Dracen Pharmaceuticals, Siemens Healthineers; institutional research support from Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche. EN: research support from Roche, Merck Serono, Bristol Myers Squibb and Pfizer and participated in advisory boards or lectures from Bristol Myers Squibb, Merck Serono, Merck Sharpe & Dohme, Lilly, Roche, Pfizer, Takeda, Bayer, Boehringer Ingelheim, Amgen and AstraZeneca. DS: Consulting, advisory role, honoraria from AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Eli Lilly; travel grants from Roche. RGC: Consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Janseen, MSD, Roche, Pfizer, Eli Lilly, Amgen, Sanofi; honoraria (self) from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Roche, MSD, Takeda, Eli Lilly, Novartis; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis. JMe: Advisory Boards/Honoraria/Speakers’ fee/Consultant for Astra-Zeneca, Boeringher Ingelheim, BMS, Roche, MSD; travel grants from Astra-Zeneca, Boeringher Ingelheim, BMS, Ipsen, Roche, MSD. VB: Clinical trial research from AstraZeneca, Roche, MSD; advisory role/consulting/speaker from Pfizer, MSD, AstraZeneca, Roche, Bristol, Merck, Takeda. MC: Advisory or Consultancy role from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, EUSA Pharma, Lilly, Roche; honoraria, lectures from Abbot, Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, Pierre Fabre, Roche; travel, expenses from Ipsen, Lilly, Merck, Pfizer, Pierre Fabre; institutional financial interests from Astra Zeneca, Merck, Roche, Pfizer. GR: consulting, advisory role or lectures from AstraZeneca, Bayer, Bristol-Myers Squibb, Janssen, Merck Sharp & Dome, Pfizer, Roche, Takeda; sponsored Research Amgen and Janssen. BB: sponsored research at Gustave Roussy Cancer Centre Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. DP: consulting, advisory role or lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; clinical trials research from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; travel, accommodations, expenses from AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. LM: research grant/Funding (self) from Bristol Myers Squibb, Boehringer Ingelheim, Amgen, Stilla, Inivata; advisory/consultancy from Roche, Takeda; honoraria (self) from Bristol Myers Squibb, Roche, Takeda, AstraZeneca; travel/Accommodation/Expenses from Roche, Bristol Myers Squibb, Takeda, AstraZeneca; non-remunerated activity/ies from AstraZeneca. MR, EA, MMo, ND, EE, RL, JMo, FA, SP, AD, MSp, EM, RR, JCB, LL, BD, AdG, CAV and GL declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored., Materials and Methods: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR., Results: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRAS G12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRAS G12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRAS G12C patients tested negative for the presence of p.T790M resistance mutation., Conclusions: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRAS G12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature., Competing Interests: Disclosure VC reports personal fees from Roche, BMS, MSD and Pfizer and other from Lilly, AstraZeneca, Boehringer, Novartis and Takeda during the conduct of the study. AS-H reports personal fees and non-financial support from Roche and personal fees from AstraZeneca and Boehringer, outside the submitted work. AR reports personal fees from Boehringer and Takeda outside the submitted work. MP reports grants, personal fees and non-financial support from BMS, Roche and AstraZeneca and personal fees from MSD and Takeda, outside the submitted work. The remaining authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung cancer continues to be the leading cause of cancer mortality and a serious health problem despite the numerous advances made in the last decade and the rapid advance of research in this field. In recent years, there has been a decrease in mortality from lung cancer coinciding with the approval times of targeted therapy. To date, targeted therapy has been used in the context of advanced disease in clinical practice, with great benefits in survival and quality of life. The next step will be to incorporate targeted therapy into the treatment of earlier stages of non-small-cell lung cancer, and there is already a randomized trial showing a disease-free survival benefit. However, there are many questions that need to be resolved first. In the present review, the authors discuss the findings of published reports and ongoing clinical trials assessing the role of targeted therapies in nonmetastatic disease.

Background: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need., Patients and Methods: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry., Results: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months)., Conclusion: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD-1), has shown promising results in patients with advanced malignancies, including melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs) have been reported, including both organ-specific toxicities and skin toxicities. Herein, we report a case of predominantly palmoplantar psoriasis with severe nail involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving nivolumab treatment for lung cancer. We also summarize the case reports that have been published previously. The knowledge of these irAEs in patients undergoing anti-PD1 therapy is important since it will enable earlier recognition and appropriate management, with the aim of maintaining effective dose without disruption.