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First-line PD-1/PD-L1 inhibitor plus chemotherapy vs chemotherapy alone for negative or < 1% PD-L1-expressing metastatic non-small-cell lung cancers

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Aims

Single-agent anti-PD-1/PD-L1 clinical efficacy against < 1% PD-L1-expressing non-small-cell lung cancers (NSCLCs) is controversial.

Methods

This meta-analysis examined randomized-trial data comparing first-line PD-1/PD-L1-inhibitor + chemotherapy (CT) vs CT alone for advanced < 1% PD-L1 NSCLCs. Outcome measures included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR).

Results

IMpower (atezolizumab + CT), Keynote (pembrolizumab + CT) and CheckMate (nivolumab + CT) trials included 2037 NSCLCs (1246 PD-L1–negative; 791 < 1% PD-L1 expression). Anti-PD-1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.75 [0.63–0.89]; p = 0.0008) and PFS (0.72 [0.65–0.80]; p < 0.0001), and higher ORR (odds ratio 2.06 [1.50–2.83]; p < 0.0001).

Conclusions

First-line anti-PD-1/PD-L1 + CT combination appears superior to CT alone for advanced, < 1% PD-L1-expressing NSCLCs for OS, PFS and ORR.

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Abbreviations

ALK:

Anaplastic lymphoma kinase

ChT:

Chemotherapy

CI:

Confidence interval

DOR:

Duration of response

EGFR:

Epidermal growth factor receptor

HR:

Hazard ratio

ICI:

Immune-checkpoint inhibitor

NSCLC:

Non-small-cell lung cancer

Nsq:

Non-squamous cell

OR:

Odds ratio

ORR:

Objective response rate

OS:

Overall survival

PD-1:

Programmed cell-death protein-1

PD-L1:

Programmed cell-death protein-1 ligand

PFS:

Progression-free survival

Sq:

Squamous cell

References

  • 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

    Article  CAS  Google Scholar 

  • Borghaei H, Hellmann MD, Paz-Ares LG, Ramalingam SS, Reck M, O’Byrne KJ et al (2018) Nivolumab (Nivo) + platinum-doublet chemotherapy (Chemo) vs chemo as first-line (1L) treatment (Tx) for advanced non-small cell lung cancer (NSCLC) with < 1% tumor PD-L1 expression: results from CheckMate 227. J Clin Oncol. 36(15_suppl):9001

    Article  Google Scholar 

  • Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373(2):123–135

    Article  CAS  Google Scholar 

  • Cappuzzo F, McCleod M, Hussein M, Morabito A, Rittmeyer A, Conter HJ et al (2018) LBA53IMpower130: progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC. Ann Oncol. https://doi.org/10.1093/annonc/mdy424.065

    Article  PubMed  Google Scholar 

  • Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M et al (2017) First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 376(25):2415–2426

    Article  CAS  Google Scholar 

  • Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 378:2078–2092

    Article  CAS  Google Scholar 

  • Heinhuis KM, Ros W, Kok M, Steeghs N, Beijnen JH, Schellens JHM (2019) Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors. Ann Oncol 30(2):219–235

    Article  CAS  Google Scholar 

  • Hellmann MD, Ciuleanu T-E, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C et al (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378:2093–2104

    Article  CAS  Google Scholar 

  • Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y et al (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet Lond Engl 387(10027):1540–1550

    Article  CAS  Google Scholar 

  • Jotte RM, Cappuzzo F, Vynnychenko I, Stroyakovskiy D, Rodriguez Abreu D, Hussein MA et al (2018) IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. 36(18):LBA9000

    Article  Google Scholar 

  • Landre T, Des Guetz G, Vergnenegre A, Chouaid C (2019) 165PClinical benefit of anti PD-1/PD-L1 plus chemotherapy versus chemotherapy alone in first-line treatment in advanced non-small cell lung cancer: a meta-analysis. Ann Oncol. https://doi.org/10.1093/annonc/mdz063.063/5445436

    Article  Google Scholar 

  • Mok T, Johnson M, Garon E, Peters S, Soria J, Wang L et al (2017) P1.04–008 POSEIDON: a phase 3 study of first-line durvalumab ± tremelimumab + chemotherapy vs chemotherapy alone in metastatic NSCLC. J Thorac Oncol 12(11):S1975

    Article  Google Scholar 

  • Mok TSK, Wu Y-L, Kudaba I, Kowalski DM, Cho BC, Turna HZ 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 Lond Engl 393(10183):1819–1830

    Article  CAS  Google Scholar 

  • Papadimitrakopoulou V, Gadgeel SM, Borghaei H, Gandhi L, Patnaik A, Powell SF et al (2017) First-line carboplatin and pemetrexed (CP) with or without pembrolizumab (pembro) for advanced nonsquamous NSCLC: Updated results of KEYNOTE-021 cohort G. J Clin Oncol 35(15_suppl):9094

    Article  Google Scholar 

  • Papadimitrakopoulou V, Cobo M, Bordoni R, Dubray-Longeras P, Szalai Z, Ursol G et al (2018) OA05.07 IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. J Thorac Oncol. 13(10):S332–S333

    Article  Google Scholar 

  • Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J et al (2018) Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 379:2040–2051

    Article  CAS  Google Scholar 

  • Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375(19):1823–1833

    Article  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542–2550

    Article  CAS  Google Scholar 

  • 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 378:2288–2301

    Article  CAS  Google Scholar 

  • Wang X-J, Lin J-Z, Yu S-H, Wu S-X, Luo H-S, Du Z-S et al (2019) First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis. Immunotherapy 11(4):311–320

    Article  CAS  Google Scholar 

  • Zhou Y, Chen C, Zhang X, Fu S, Xue C, Ma Y et al (2018) Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis. J Immunother Cancer 6(1):155

    Article  Google Scholar 

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Authors and Affiliations

  1. UCOG 93, Hôpital René-Muret, APHP, Sevran, France

    Thierry Landre

  2. Service d’Oncologie Médicale, Centre Hospitalier Delafontaine, Saint-Denis, France

    Gaetan Des Guetz

  3. Service d’Oncologie Médicale, Hôpital Avicenne, APHP, Bobigny, France

    Kader Chouahnia

  4. Service d’Oncogériatrie, Hôpital René-Muret, APHP, Sevran, France

    Cherifa Taleb

  5. Service d’Oncologie Médicale, Unité d’Oncologie Thoracique, Limoges, France

    Alain Vergnenègre

  6. Service de Pneumologie, Centre Hospitalier Intercommunal (CHI) Créteil, Créteil, France

    Christos Chouaïd

Authors
  1. Thierry Landre
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  2. Gaetan Des Guetz
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  3. Kader Chouahnia
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  4. Cherifa Taleb
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  5. Alain Vergnenègre
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  6. Christos Chouaïd
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Correspondence to Thierry Landre.

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Landre, T., Des Guetz, G., Chouahnia, K. et al. First-line PD-1/PD-L1 inhibitor plus chemotherapy vs chemotherapy alone for negative or < 1% PD-L1-expressing metastatic non-small-cell lung cancers. J Cancer Res Clin Oncol 146, 441–448 (2020). https://doi.org/10.1007/s00432-019-03070-3

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  • DOI: https://doi.org/10.1007/s00432-019-03070-3

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