17 augustus 2023: Bron: The Lancet

Voor patiënten met niet-kleincellige longkanker (NSCLC) die niet in aanmerking komen voor op platina gebaseerde dubbele chemokuur, geeft immuuntherapie als eerstelijns behandeling met alleen anti-PD medicijn atezolizumab een verbeterde algehele overleving in vergelijking met chemotherapie met 1 medicijn. Na 2 jaar was met alleen atezolizumab nog 24 procent van de deelnemende patiënten in leven tegenover 12 procent met alleen 1 chemokuur. Ook de ernstige bijwerkingen waren minder voor atezolizumab (16 vs 33 procent) . En minder aan behandeling gerelateerde sterfgevallen (1 vs 3 procent).

Siow Ming Lee, M.B.B.S., Ph.D., en collega's van het University College London, voerden deze gerandomiseerde gecontroleerde fase III studie  uit op 91 locaties in 23 landen om de werkzaamheid en veiligheid van eerstelijns monotherapie met atezolizumab te vergelijken met chemotherapie met één middel bij patiënten met stadium IIIB of IV niet-kleincellige longkanker (NSCLC) bij wie op platina gebaseerde dubbele chemotherapie ongeschikt werd geacht.
In totaal werden 453 patiënten ingeschreven en willekeurig toegewezen aan atezolizumab of chemotherapie (respectievelijk 302 en 151 patiënten).

De onderzoekers ontdekten dat atezolizumab in vergelijking met chemotherapie de algehele overleving verbeterde (mediane totale overleving, 10,3 versus 9,2 maanden; gestratificeerde hazard ratio, 0,78), met een overlevingspercentage van twee jaar van 24 procent met atezolizumab en 12 procent met chemotherapie.

Atezolizumab werd geassocieerd met stabilisatie of verbetering van door de patiënt gerapporteerde gezondheidsgerelateerde kwaliteit van leven functionerende schalen en symptomen in vergelijking met chemotherapie, en met minder graad 3 tot 4 behandelingsgerelateerde bijwerkingen (16 versus 33 procent) en behandelingsgerelateerde sterfgevallen (1 versus 3 procent).

Als conclusie schrijven de auteurs:

"Eerstelijns atezolizumab werd in verband gebracht met een verbeterde overleving en een verdubbeling van de overlevingskans na twee jaar, ondanks dat meer dan 50 procent van de patiënten in de chemotherapie groep na twee jaar nog in leven was en daaropvolgende immuuntherapie kreeg", schrijven de auteurs.

Het volledige studierapport is tegen betaling in te zien. Hier het abstract uit the Lancet:

ARTICLES| VOLUME 402, ISSUE 10400P451-463, AUGUST 05, 2023

First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study



Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy.


This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0–1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine ; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786.


Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4–11·9] vs 9·2 months [5·9–11·2]; stratified hazard ratio 0·78 [0·63–0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3–29·4) with atezolizumab compared with 12% (6·7–18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3–4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]).


First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy.


F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.


  1. 1.
    • Grant MJ 
    • Herbst RS 
    • Goldberg SB
    Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC.
    Nat Rev Clin Oncol. 2021; 18625-644
  2. 2.
    • Hanna NH 
    • Schneider BJ 
    • Temin S 
    • et al.
    Therapy for stage IV non-small-cell lung cancer without driver alterations: ASCO and OH (CCO) Joint Guideline Update.
    J Clin Oncol. 2020; 381608-1632
  3. 3.
    • Planchard D 
    • Popat S 
    • Kerr K 
    • et al.
    Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up.
    Ann Oncol. 2018; 29iv192-iv237
  4. 4.
    • Rashdan S 
    • Gerber DE
    Immunotherapy for non-small cell lung cancer: from clinical trials to real-world practice.
    Transl Lung Cancer Res. 2019; 8202-207
  5. 5.
    • Quoix E 
    • Zalcman G 
    • Oster J-P 
    • et al.
    Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.
    Lancet. 2011; 3781079-1088
  6. 6.
    • Lilenbaum RC 
    • Herndon 2nd, JE 
    • List MA 
    • et al.
    Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).
    J Clin Oncol. 2005; 23190-196
  7. 7.
    • De Marinis F 
    • Bria E 
    • Baas P 
    • et al.
    Treatment of unfit patients with advanced non-small-cell lung cancer: definition criteria according an expert panel.
    Clin Lung Cancer. 2015; 16399-405
  8. 8.
    • Royal College of Physicians
    National Lung Cancer Audit annual report 2022.
    Date: Jan 13, 2022
    Date accessed: November 29, 2022
  9. 9.
    • Tagliamento M 
    • Frelaut M 
    • Baldini C 
    • et al.
    The use of immunotherapy in older patients with advanced non-small cell lung cancer.
    Cancer Treat Rev. 2022; 106102394
  10. 10.
    • National Cancer Institute
    Surveillance, Epidemiology, and End Results Program. Cancer stat facts: lung and bronchus cancer.
    Date accessed: October 13, 2022
  11. 11.
    • Lilenbaum RC 
    • Cashy J 
    • Hensing TA 
    • Young S 
    • Cella D
    Prevalence of poor performance status in lung cancer patients: implications for research.
    J Thorac Oncol. 2008; 3125-129
  12. 12.
    • Rittmeyer A 
    • Barlesi F 
    • Waterkamp D 
    • et al.
    Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.
    Lancet. 2017; 389255-265
  13. 13.
    • Fehrenbacher L 
    • Spira A 
    • Ballinger M 
    • et al.
    Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.
    Lancet. 2016; 3871837-1846
  14. 14.
    • Herbst RS 
    • Giaccone G 
    • de Marinis F 
    • et al.
    Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC.
    N Engl J Med. 2020; 3831328-1339
  15. 15.
    • Gounant V 
    • Lavolé A 
    • Quoix E
    Ongoing challenges of using immunotherapy in special populations: poor performance status patients, elderly patients, and people living with HIV.
    Lung Cancer. 2020; 14571-75
  16. 16.
    • Schiller JH 
    • Harrington D 
    • Belani CP 
    • et al.
    Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
    N Engl J Med. 2002; 34692-98
  17. 17.
    • Carmichael JA 
    • Wing-San Mak D 
    • O'Brien M
    A review of recent advances in the treatment of elderly and poor performance NSCLC.
    Cancers (Basel). 2018; 10236
  18. 18.
    • Middleton G 
    • Brock K 
    • Savage J 
    • et al.
    Pembrolizumab in patients with non-small-cell lung cancer of performance status 2 (PePS2): a single arm, phase 2 trial.
    Lancet Respir Med. 2020; 8895-904
  19. 19.
    • Barlesi F 
    • Audigier-Valette C 
    • Felip E 
    • et al.
    OA04.02 CheckMate 817: first-line nivolumab + ipilimumab in patients with ECOG PS 2 and other special populations with advanced NSCLC.
    J Thorac Oncol. 2019; 14S214-S215
  20. 20.
    • Lena H 
    • Monnet I 
    • Bylicki O 
    • et al.
    Randomized phase III study of nivolumab and ipilimumab versus carboplatin-based doublet in first-line treatment of PS 2 or elderly (≥70 years) patients with advanced non-small-cell lung cancer (Energy-GFPC 06-2015 study).
    J Clin Oncol. 2022; 409011
  21. 21.
    • Mark M 
    • Froesch P 
    • Eboulet EI 
    • et al.
    SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced non-small-cell lung cancer and a performance status of 2.
    Cancer Immunol Immunother. 2021; 701255-1262
  22. 22.
    • Kwan TY 
    • Chowdhury EH
    Clinical outcomes of chemotherapeutic molecules as single and multiple agents in advanced non-small-cell lung carcinoma (NSCLC) patients.
    Medicina (Kaunas). 2021; 571252
  23. 23.
    • Rudd RM 
    • Gower NH 
    • Spiro SG 
    • et al.
    Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.
    J Clin Oncol. 2005; 23142-153
  24. 24.
    • Lee SM 
    • Rudd R 
    • Woll PJ 
    • et al.
    Randomized double-blind placebo-controlled trial of thalidomide in combination with gemcitabine and carboplatin in advanced non-small-cell lung cancer.
    J Clin Oncol. 2009; 275248-5254
  25. 25.
    • Bronte G 
    • Rolfo C 
    • Passiglia F 
    • et al.
    What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis.
    Crit Rev Oncol Hematol. 2015; 95306-317
  26. 26.
    • O'Brien MER 
    • Socinski MA 
    • Popovich AY 
    • et al.
    Randomized phase III trial comparing single-agent paclitaxel poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer.
    J Thorac Oncol. 2008; 3728-734
  27. 27.
    • Su C 
    • Zhou F 
    • Shen J 
    • Zhao J 
    • O'Brien M
    Treatment of elderly patients or patients who are performance status 2 (PS2) with advanced non-small-cell lung cancer without epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations—still a daily challenge.
    Eur J Cancer. 2017; 83266-278
  28. 28.
    • Camerini A 
    • Puccetti C 
    • Donati S 
    • et al.
    Metronomic oral vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer: results of a phase II trial (MOVE trial).
    BMC Cancer. 2015; 15359
  29. 29.
    • Reck M 
    • Popat S 
    • Reinmuth N 
    • De Ruysscher D 
    • Kerr KM 
    • Peters S
    Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up.
    Ann Oncol. 2014; 25iii27-iii39
  30. 30.
    • Camerini A 
    • Del Conte A 
    • Pezzuto A 
    • et al.
    Selection criteria and treatment outcome for advanced non-small-cell lung cancer (NSCLC) patients unfit for platinum-based first-line therapy: results of the MOON-OSS observational trial.
    Cancers (Basel). 2022; 146074
  31. 31.
    • Ahn MJ 
    • D'Cruz A 
    • Vermorken JB 
    • et al.
    Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: a literature review.
    Oral Oncol. 2016; 5310-16

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