Anti-PD-(L)1 for KRAS-mutant advanced non-small-cell lung cancers: a meta-analysis of randomized-controlled trials.
B7-H1 Antigen
/ antagonists & inhibitors
Carcinoma, Non-Small-Cell Lung
/ diagnosis
Disease Management
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Lung Neoplasms
/ diagnosis
Molecular Targeted Therapy
Mutation
Proportional Hazards Models
Proto-Oncogene Proteins p21(ras)
/ genetics
Randomized Controlled Trials as Topic
Retreatment
Treatment Outcome
Immunotherapy
KRAS
Meta-analysis
Non-small-cell lung cancer
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
14
04
2021
accepted:
04
08
2021
pubmed:
12
8
2021
medline:
1
3
2022
entrez:
11
8
2021
Statut:
ppublish
Résumé
The most frequent mutation in advanced non-small-cell lung cancer (NSCLC), Kirsten rat-sarcoma viral oncogene (KRAS) is found in 20-25% of these patients' tumors. While phase III trials on therapies targeting KRAS, especially KRAS This meta-analysis examined randomized-trial data comparing first- or second-line anti-PD-(L)1 with or without chemotherapy vs. chemotherapy alone for advanced KRAS-mutant NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). We analyzed 3 first-line trials (IMpower-150, Keynote-189 and Keynote-042) and 3 second-line trials (Oak, Poplar and CheckMate-057) that included 1313 NSCLCs (386 KRAS-mutant and 927 KRAS wild-type tumors). For KRAS-mutant NSCLCs, anti-PD-(L)1 with or without chemotherapy was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to chemotherapy alone. OS benefited in both first- and second-line trials. OS for patients with KRAS-mutant NSCLCs was significantly longer than that for those with KRAS wild-type tumors (p = 0.001). Anti-PD-(L)1 with or without chemotherapy seemed to achieve longer OS and PFS than chemotherapy alone for patients with KRAS-mutant and wild-type KRAS advanced NSCLCs, with an even greater OS benefit for the former.
Identifiants
pubmed: 34378081
doi: 10.1007/s00262-021-03031-1
pii: 10.1007/s00262-021-03031-1
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
KRAS protein, human
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
719-726Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C et al (2018) Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol. 29(Suppl 4):192–237
doi: 10.1093/annonc/mdy275
El Osta B, Behera M, Kim S, Berry LD, Sica G, Pillai RN et al (2019) Characteristics and outcomes of patients with metastatic kras-mutant lung adenocarcinomas: the lung cancer mutation consortium experience. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 14(5):876–889
Jordan EJ, Kim HR, Arcila ME, Barron D, Chakravarty D, Gao J et al (2017) Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov juin 7(6):596–609
doi: 10.1158/2159-8290.CD-16-1337
Dogan S, Shen R, Ang DC, Johnson ML, D’Angelo SP, Paik PK et al (2012) Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res Off J Am Assoc Cancer Res 18(22):6169–6177
doi: 10.1158/1078-0432.CCR-11-3265
Goulding RE, Chenoweth M, Carter GC, Boye ME, Sheffield KM, John WJ et al (2020) KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: a systematic literature review and meta-analysis. Cancer Treat Res Commun 24:100200
doi: 10.1016/j.ctarc.2020.100200
Agyeman A, Vallejo JJ, Myers A, Blumenthal GM. (2018). Meta-analysis exploring the effect of oncogenic driver mutations on outcome of metastatic non-small cell lung cancer (mNSCLC) patients (pts) treated with immune checkpoint inhibitors (ICI) or docetaxel (doc). J Clin Oncol. 36(15_suppl): 9029‑9029.
Torralvo J, Friedlaender A, Achard V, Addeo A (2019) The activity of immune checkpoint inhibition in kras mutated non-small cell lung cancer: a single centre experience. Cancer Genomics Proteomics 16(6):577–582
doi: 10.21873/cgp.20160
Lee CK, Man J, Lord S, Cooper W, Links M, Gebski V et al (2018) Clinical and molecular characteristics associated with survival among patients treated with checkpoint inhibitors for advanced non-small cell lung carcinoma: a systematic review and meta-analysis. JAMA Oncol 4(2):210–216
doi: 10.1001/jamaoncol.2017.4427
Nishio M, Barlesi F, West H, Ball S, Bordoni R, Cobo M, et al. (2020). Atezolizumab Plus Chemotherapy for First-Line Treatment of Non-Squamous Non-Small Cell Lung Cancer: Results From the Randomized Phase III IMpower132 Trial. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer.
West H, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ et al (2019) Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol juill 20(7):924–937
doi: 10.1016/S1470-2045(19)30167-6
Herbst RS, Lopes G, Kowalski DM, Kasahara K, Wu Y-L, Castro GD et al (2019) LBA4 Association of KRAS mutational status with response to pembrolizumab monotherapy given as first-line therapy for PD-L1-positive advanced non-squamous NSCLC in Keynote-042. Ann Oncol 30:xi63–xi64
doi: 10.1093/annonc/mdz453.001
Gadgeel S, Rodriguez-Abreu D, Felip E, Esteban E, Speranza G, Reck M et al (2019) LBA5–KRAS mutational status and efficacy in KEYNOTE-189: Pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC. Ann Oncol 30:xi64–xi65
doi: 10.1093/annonc/mdz453.002
Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N et al (2018) Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 378(24):2288–2301
doi: 10.1056/NEJMoa1716948
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373(17):1627–1639
doi: 10.1056/NEJMoa1507643
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J et al (2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet Lond Engl 387(10030):1837–1846
doi: 10.1016/S0140-6736(16)00587-0
Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J et al (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet Lond Engl. 389(10066):255–265
doi: 10.1016/S0140-6736(16)32517-X
Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L et al (2019) Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol Off J Eur Soc Med Oncol 30(8):1321–1328
doi: 10.1093/annonc/mdz167
Ng TL, Liu Y, Dimou A, Patil T, Aisner DL, Dong Z et al (2019) Predictive value of oncogenic driver subtype, programmed death-1 ligand (PD-L1) score, and smoking status on the efficacy of PD-1/PD-L1 inhibitors in patients with oncogene-driven non-small cell lung cancer. Cancer 125(7):1038–1049
doi: 10.1002/cncr.31871
Scheel AH, Ansén S, Schultheis AM, Scheffler M, Fischer RN, Michels S et al (2016) PD-L1 expression in non-small cell lung cancer: correlations with genetic alterations. Oncoimmunology 5(5):e1131379
doi: 10.1080/2162402X.2015.1131379
Jeanson A, Tomasini P, Souquet-Bressand M, Brandone N, Boucekine M, Grangeon M et al (2019) Efficacy of Immune checkpoint inhibitors in kras-mutant non-small cell lung cancer (NSCLC). J Thorac Oncol Off Publ Int Assoc Study Lung Cancer 14(6):1095–1101
Aredo JV, Padda SK, Kunder CA, Han SS, Neal JW, Shrager JB et al (2019) Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes. Lung Cancer Amst Neth juill 133:144–150
doi: 10.1016/j.lungcan.2019.05.015
Arbour KC, Rizvi H, Plodkowski AJ, Hellmann MD, Knezevic A, Heller G, et al. Treatment Outcomes and Clinical Characteristics of Patients with KRAS-G12C-Mutant Non-Small Cell Lung Cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 8 févr;
Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI et al (2020) KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 383(13):1207–1217
doi: 10.1056/NEJMoa1917239