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17 november 2022: Bron: FDA

De FDA - Amerikaanse Food and Drug Administration heeft na uitstekende resultaten uit de fase III Posseidon studie de combinatiebehandeling van het anti-PD medicijn tremelimumab (Imjudo) plus het monoklonaal anti-lichaamsmedicijn durvalumab (Imfinzi) en op platina gebaseerde chemotherapie goedgekeurd voor volwassen patiënten met vergevorderde niet-kleincellige longkanker waarbij geen mutaties zijn aangetoond van een EGFR-mutatie of van een ALK afwijking (anaplastisch lymfoomkinase).

Uit de Posseidon studie met totaal 675 patiënten blijkt dat de mediane totale overleving was 14 maanden met tremelimumab plus durvalumab en 11,7 maanden met alleen op platina gebaseerde chemotherapie. De mediane progressievrije overleving was respectievelijk 6,2 maanden en 4,8 maanden (hazard ratio 0,72). Het totale responspercentage was 39 procent met de medicijncombinatie versus 24 procent met alleen chemotherapie, met een mediane responsduur van respectievelijk 9,5 en 5,1 maanden.

Zowel tremelimumab als durvalumab worden toegediend als intraveneuze infusie. Voor patiënten die 30 kg of meer wegen, is de aanbevolen dosis tremelimumab 75 mg om de drie weken met 1500 mg durvalumab en chemotherapie op basis van platina gedurende vier cycli, daarna 1500 mg durvalumab met onderhoudschemotherapie om de vier weken. Een vijfde dosis tremelimumab (75 mg) moet in week 16 worden gegeven.

Voor de FDA goedkeuring klik op deze link:

FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer

Studieverslag is gratis in te zien. Klik op de titel van het abstract:

2022 Apr; 7(2): 100408.

Published online 2022 Mar 10. doi: 10.1016/j.esmoop.2022.100408

PMCID: PMC9161394

PMID: 35279527

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN*

L. Paz-Ares,1,∗ Y. Chen,2 N. Reinmuth,3 K. Hotta,4 D. Trukhin,5 G. Statsenko,6 M.J. Hochmair,7 M. Özgüroğlu,8 J.H. Ji,9 M.C. Garassino,10,11 O. Voitko,12 A. Poltoratskiy,13 E. Musso,14 L. Havel,15 I. Bondarenko,16 G. Losonczy,17 N. Conev,18 H. Mann,19 T.B. Dalvi,20 H. Jiang,20 and J.W. Goldman21

Author information Copyright and License information Disclaimer

Associated Data

Supplementary Materials

Abstract

Background

In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of >3 years.

Patients and methods

805 patients with treatment-naïve ES-SCLC were randomized 1 : 1 : 1 to durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP. The two primary endpoints were OS for durvalumab plus EP versus EP and for durvalumab plus tremelimumab plus EP versus EP.

Results

As of 22 March 2021 (median follow-up 39.4 months, 86% maturity), durvalumab plus EP continued to demonstrate improved OS versus EP: hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.60-0.86; nominal P = 0.0003]; median OS was 12.9 versus 10.5 months, and 36-month OS rate was 17.6% versus 5.8%. Durvalumab plus tremelimumab plus EP continued to numerically improve OS versus EP: HR 0.81 (95% CI: 0.67-0.97; nominal P = 0.0200); median OS was 10.4 months, and 36-month OS rate was 15.3%. Twenty-seven and nineteen patients in the durvalumab plus EP and durvalumab plus tremelimumab plus EP arms, respectively, remained on durvalumab treatment at data cut-off.

Conclusions

Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP, with the majority still receiving durvalumab at data cut-off, further establishing durvalumab plus EP as first-line standard of care for ES-SCLC.

Cited by

Neuroendocrine neoplasms of the lung and gastrointestinal system: convergent biology and a path to better therapies.
Kawasaki K, Rekhtman N, Quintanal-Villalonga Á, Rudin CM.Nat Rev Clin Oncol. 2022 Oct 28. doi: 10.1038/s41571-022-00696-0. Online ahead of print.PMID: 36307533 Review.
Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial.
Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group.JAMA. 2022 Sep 27;328(12):1223-1232. doi: 10.1001/jama.2022.16464.PMID: 36166026 Clinical Trial.
Efficacy and Safety of Amrubicin in Small Cell Carcinoma Previously Treated with Immune Checkpoint Inhibitors and Chemotherapy.
Nishimura T, Fujimoto H, Fujiwara T, Ito K, Fujiwara A, Yuda H, Itani H, Naito M, Kodama S, Yagi A, D'Alessandro VF, Yasuma T, Furuhashi K, Saiki H, Okano T, Tomaru A, Tanigawa M, D'Alessandro-Gabazza CN, Gabazza EC, Yoshida M, Hataji O, Ibata H, Kobayashi T.Cancers (Basel). 2022 Aug 16;14(16):3953. doi: 10.3390/cancers14163953.PMID: 36010946 Free PMC article.
Impact of Socioeconomic Factors on Overall Survival in SCLC.
Roof L, Wei W, Tullio K, Pennell NA, Stevenson JP.JTO Clin Res Rep. 2022 Jun 18;3(7):100360. doi: 10.1016/j.jtocrr.2022.100360. eCollection 2022 Jul.PMID: 35815321 Free PMC article.
Impact of Brain Metastases on Treatment Patterns and Outcomes With First-Line Durvalumab Plus Platinum-Etoposide in Extensive-Stage SCLC (CASPIAN): A Brief Report.
Chen Y, Paz-Ares L, Reinmuth N, Garassino MC, Statsenko G, Hochmair MJ, Özgüroğlu M, Verderame F, Havel L, Losonczy G, Conev NV, Hotta K, Ji JH, Spencer S, Dalvi T, Jiang H, Goldman JW.JTO Clin Res Rep. 2022 Apr 26;3(6):100330. doi: 10.1016/j.jtocrr.2022.100330. eCollection 2022 Jun.PMID: 35719865 Free PMC article.

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