Top

Published in:

Open Access 24-01-2023 | NSCLC | Research

Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50%

Authors: E. Pons-Tostivint, P. Hulo, V. Guardiolle, L. Bodot, A. Rabeau, M. Porte, S. Hiret, P. Demontrond, H. Curcio, A. Boudoussier, R. Veillon, M. Mayenga, C. Dumenil, T. Chatellier, P. A. Gourraud, J. Mazieres, J. Bennouna

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

Abstract

Introduction

Pembrolizumab alone (IO-mono) or in combination with platinum-based chemotherapy (CT-IO) is first-line standard of care for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. This retrospective multicentre study assessed real-world use and efficacy of both strategies.

Methods

Patients with advanced NSCLC PD-L1 ≥ 50% from eight hospitals who had received at least one cycle of IO-mono or CT-IO were included. Overall survival (OS) and real-word progression-free-survival were estimated using Kaplan–Meier methodology. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, and a Cox model with inverse propensity treatment weighting was carried out.

Results

Among the 243 patients included, 141 (58%) received IO-mono and 102 (42%) CT-IO. Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. With a median follow-up of 11.5 months (95% CI 10.4–13.3), median OS was not reached, but no difference was observed between groups (p = 0.51). Early deaths at 12 weeks were 11% (95% CI 4.6–16.9) and 15.2% (95% CI 9.0–20.9) in CT-IO and IO groups (p = 0.32). After adjustment for age, gender, performance status, histology, brain metastases, liver metastases and tobacco status, no statistically significant difference was found for OS between groups, neither in the multivariate adjusted model [HR 1.07 (95% CI 0.61–1.86), p = 0.8] nor in propensity adjusted analysis [HR 0.99 (95% CI 0.60–1.65), p = 0.99]. Male gender (HR 2.01, p = 0.01) and PS ≥ 2 (HR 3.28, p < 0.001) were found to be negative independent predictive factors for OS.

Conclusion

Younger patients, those with symptomatic disease and brain metastases were more likely to be proposed CT-IO. However, sparing the chemotherapy in first-line does not appear to impact survival outcomes, even regarding early deaths.

Available only for authorised users

Reck M, Rodríguez-Abreu D, Robinson AG et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833. https://doi.org/10.1056/NEJMoa1606774CrossRefPubMed

Mok TSK, Wu Y-L, Kudaba I et al (2019) Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393:1819–1830. https://doi.org/10.1016/S0140-6736(18)32409-7CrossRefPubMed

Herbst RS, Giaccone G, de Marinis F et al (2020) Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med 383:1328–1339. https://doi.org/10.1056/NEJMoa1917346CrossRefPubMed

Sezer A, Kilickap S, Gümüş M et al (2021) Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet 397:592–604. https://doi.org/10.1016/S0140-6736(21)00228-2CrossRefPubMed

Reck M, Rodríguez-Abreu D, Robinson AG et al (2021) Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol 39:2339–2349. https://doi.org/10.1200/JCO.21.00174CrossRefPubMedPubMedCentral

Planchard D, Popat S, Kerr K et al (2018) Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29:iv192–iv237. https://doi.org/10.1093/annonc/mdy275

Ettinger DS, Wood DE, Aisner DL et al (2022) Non-small cell lung cancer, version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 20:497–530. https://doi.org/10.6004/jnccn.2022.0025CrossRefPubMed

Doroshow DB, Bhalla S, Beasley MB et al (2021) PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol 18:345–362. https://doi.org/10.1038/s41571-021-00473-5CrossRefPubMed

Ferrara R, Mezquita L, Texier M et al (2018) Hyperprogressive disease in patients with advanced non-small cell lung cancer treated with PD-1/PD-L1 inhibitors or with single-agent chemotherapy. JAMA Oncol 4:1543–1552. https://doi.org/10.1001/jamaoncol.2018.3676CrossRefPubMedPubMedCentral

10.

Ferrara R, Mezquita L, Texier M et al (2020) Comparison of fast-progression, hyperprogressive disease, and early deaths in advanced non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors or chemotherapy. JCO Precis Oncol 4:829–840. https://doi.org/10.1200/PO.20.00021CrossRefPubMed

11.

Gadgeel S, Rodríguez-Abreu D, Speranza G et al (2020) Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol 38:1505–1517. https://doi.org/10.1200/JCO.19.03136CrossRefPubMed

12.

Paz-Ares L, Vicente D, Tafreshi A et al (2020) A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with metastatic squamous NSCLC: protocol-specified final analysis of KEYNOTE-407. J Thorac Oncol 15:1657–1669. https://doi.org/10.1016/j.jtho.2020.06.015CrossRefPubMed

13.

Yang F, Markovic SN, Molina JR, et al (2020) Association of sex, age, and eastern cooperative oncology group performance status with survival benefit of cancer immunotherapy in randomized clinical trials: a systematic review and meta-analysis. JAMA Netw Open 3:e2012534. https://doi.org/10.1001/jamanetworkopen.2020.12534

14.

El-Osta H, Jafri S (2019) Predictors for clinical benefit of immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis. Immunotherapy 11:189–199. https://doi.org/10.2217/imt-2018-0086CrossRefPubMed

15.

Cortellini A, Tiseo M, Banna GL et al (2020) Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cancer Immunol Immunother 69:2209–2221. https://doi.org/10.1007/s00262-020-02613-9CrossRefPubMed

16.

Gainor JF, Rizvi H, Jimenez Aguilar E et al (2020) Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50. Ann Oncol 31:404–411. https://doi.org/10.1016/j.annonc.2019.11.015CrossRefPubMed

17.

Conforti F, Pala L, Pagan E, et al (2021) Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials. ESMO Open 6:100251. https://doi.org/10.1016/j.esmoop.2021.100251

18.

Facchinetti F, Mazzaschi G, Barbieri F et al (2020) First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status. Eur J Cancer 130:155–167. https://doi.org/10.1016/j.ejca.2020.02.023CrossRefPubMed

19.

Velcheti V, Chandwani S, Chen X et al (2019) Outcomes of first-line pembrolizumab monotherapy for PD-L1-positive (TPS ≥50%) metastatic NSCLC at US oncology practices. Immunotherapy 11:1541–1554. https://doi.org/10.2217/imt-2019-0177CrossRefPubMed

20.

Tamiya M, Tamiya A, Hosoya K et al (2019) Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001). Investig New Drugs 37:1266–1273. https://doi.org/10.1007/s10637-019-00843-yCrossRefPubMed

21.

Waterhouse D, Lam J, Betts KA et al (2021) Real-world outcomes of immunotherapy-based regimens in first-line advanced non-small cell lung cancer. Lung Cancer 156:41–49. https://doi.org/10.1016/j.lungcan.2021.04.007CrossRefPubMed

22.

Passaro A, Spitaleri G, Gyawali B, de Marinis F (2019) Immunotherapy in non-small-cell lung cancer patients with performance status 2: clinical decision making with scant evidence. JCO 37:1863–1867. https://doi.org/10.1200/JCO.18.02118CrossRef

23.

Middleton G, Brock K, Savage J et al (2020) Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial. Lancet Respir Med 8:895–904. https://doi.org/10.1016/S2213-2600(20)30033-3CrossRefPubMed

24.

Powell SF, Rodríguez-Abreu D, Langer CJ et al (2021) Outcomes with pembrolizumab plus platinum-based chemotherapy for patients with NSCLC and stable brain metastases: pooled analysis of KEYNOTE-021, -189, and -407. J Thorac Oncol 16:1883–1892. https://doi.org/10.1016/j.jtho.2021.06.020CrossRefPubMed

25.

Mansfield AS, Herbst RS, de Castro G et al (2021) Outcomes with pembrolizumab monotherapy in patients with programmed death-ligand 1-positive NSCLC with brain metastases: pooled analysis of KEYNOTE-001, 010, 024, and 042. JTO Clin Res Rep 2:100205. https://doi.org/10.1016/j.jtocrr.2021.100205

26.

Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16:626–638. https://doi.org/10.1038/nri.2016.90CrossRefPubMed

27.

Cook MB, McGlynn KA, Devesa SS et al (2011) Sex disparities in cancer mortality and survival. Cancer Epidemiol Biomark Prev 20:1629–1637. https://doi.org/10.1158/1055-9965.EPI-11-0246CrossRef

28.

Yu XQ, Yap ML, Cheng ES et al (2022) Evaluating prognostic factors for sex differences in lung cancer survival: findings from a large Australian cohort. J Thorac Oncol 17:688–699. https://doi.org/10.1016/j.jtho.2022.01.016CrossRefPubMed

29.

Conforti F, Pala L, Pagan E et al (2021) Sex-based dimorphism of anticancer immune response and molecular mechanisms of immune evasion. Clin Cancer Res 27:4311–4324. https://doi.org/10.1158/1078-0432.CCR-21-0136CrossRefPubMedPubMedCentral

30.

Conforti F, Pala L, Bagnardi V et al (2019) Sex-based heterogeneity in response to lung cancer immunotherapy: a systematic review and meta-analysis. J Natl Cancer Inst 111:772–781. https://doi.org/10.1093/jnci/djz094CrossRefPubMedPubMedCentral

31.

Pérol M, Felip E, Dafni U et al (2022) Effectiveness of PD-(L)1 inhibitors alone or in combination with platinum-doublet chemotherapy in first-line (1L) non-squamous non-small-cell lung cancer (Nsq-NSCLC) with PD-L1-high expression using real-world data. Ann Oncol 33:511–521. https://doi.org/10.1016/j.annonc.2022.02.008CrossRefPubMed

32.

Chen D-L, Li Q-Y, Tan Q-Y (2021) Smoking history and the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Dis 13:220–231. https://doi.org/10.21037/jtd-20-1953

33.

Veccia A, Sforza V, Vattemi E et al (2021) Pretreatment lung immune prognostic index as a biomarker in advanced non-small-cell lung cancer patients receiving first line pembrolizumab. Immunotherapy 13:1093–1103. https://doi.org/10.2217/imt-2021-0002CrossRefPubMed

Title: Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50%
Authors: E. Pons-Tostivint
P. Hulo
V. Guardiolle
L. Bodot
A. Rabeau
M. Porte
S. Hiret
P. Demontrond
H. Curcio
A. Boudoussier
R. Veillon
M. Mayenga
C. Dumenil
T. Chatellier
P. A. Gourraud
J. Mazieres
J. Bennouna
Publication date: 24-01-2023
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Metastasis
NSCLC
Cytostatic Therapy
Published in: Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-022-03359-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2023

Correction to: Real-world multicentre cohort of first-line pembrolizumab alone or in combination with platinum-based chemotherapy in non-small cell lung cancer PD-L1 ≥ 50%

Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with perihilar cholangiocarcinoma at high risk of recurrence

Preventive effect of tertiary lymphoid structures on lymph node metastasis of lung adenocarcinoma

First-line therapy for elderly patients with advanced renal cell carcinoma in the immuno-oncology era: a network meta-analysis

Different effects of NK cells and NK-derived soluble factors on cell lines derived from primary or metastatic pancreatic cancers

Response to neoadjuvant immune checkpoint inhibitors and chemotherapy in Chinese patients with esophageal squamous cell carcinoma: the role of tumor immune microenvironment

Keynote webinar | Spotlight on antibody–drug conjugates in cancer