Mocht u de informatie op onze website kanker-actueel.nl waarderen dan wilt u ons misschien ondersteunen met een donatie? 

Ons rekeningnummer is: RABO 37.29.31.138 t.n.v. Stichting Gezondheid Actueel in Terneuzen. 

Onze IBANcode is NL79 RABO 0372 9311 38

Als donateur kunt u ook korting krijgen bij verschillende bedrijven.

En we hebben een ANBI status

19 mei 2020: Bron: European journal of Cancer

Uit de eerste resultaten van een deelstudie uit de KEYNOTE-659 phase IIb study bij patiënten met kanker in de overgang van maag en slokdarm (bovenste gedeelte darmkanaal) blijkt dat wanneer pembrolizumab wordt gegeven naast S-1 (een combinatie van tegafur, gimeracil en oteracil) en oxalipltin (SOS genoemd afgekort) als eerstelijns behandeling dat de resultaten hoopvol en beheersbaar zijn wat betreft bijwerkingen.

72 procent van de 54 deelnemende patienten bereikte een zogeheten objectieve respons wat betekent dat zij minimaal 50 procent tumorvermindering bereikten. 

Alle patienten hadden een positieve PD-1 expressie en een human epidermal growth factor receptor 2 (HER-2) negatieve expressie.

De mediane follow-up van de studie was 10,1 maanden.

Objectieve response (ORR):  72,2% (95% betrouwbaarheidsinterval 58,4-83,5)
Duur van remissie (DOR), 96,3% (95% BI 87,3-99,5). 
Tijd tot de remissie optrad (TTR): 1,5 maanden
Ziektevrije tijd (PFS): 9,4 maanden
Mediane overall overleving (OS) nog niet bereikt

De obejectieve remissie (ORR) was 73,9% bij patiënten met PD-L1 gecombineerde positieve score (CPS) status CPS ≥ 1 tot <10 en 71,0% bij patiënten met CPS ≥ 10

Behandelingsgerelateerde bijwerkingen (TRAE's) van graad ≥3 werden gemeld door 57,4% van de patiënten. De meest voorkomende graad 3 TRAE's waren een verlaagd aantal bloedplaatjes (14,8%), een verlaagd aantal neutrofielen (13,0%), colitis (5,6%) en bijnierinsufficiëntie (5,6%).

Aangezien de prognose voor deze groep van patiënten slecht is, zie bv dit artikel: Tumoren in bovenste deel maagdarmkanaal: nog altijd moeilijk te verteren zijn deze resultaten zeker hoopvol

Het volledige studierapport: Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study is gratis in te zien. 

Hier het abstract van de studie:

Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study

Akihito Kawazoea,
, 
Kensei Yamaguchib,
, 
Hisateru Yasuic,
, 
Yuji Negorod,
, 
Mizutomo Azumae,
, 
Kenji Amagaif,
, 
Hiroki Harag,
, 
Hideo Babah,
, 
Masahiro Tsudai,
, 
Hisashi Hosakaj,
, 
Hisato Kawakamik,
, 
Takashi Oshimal,
, 
Yasushi Omurom,
, 
Nozomu Machidan,
, 
Taito Esakio,
, 
Kazuhiro Yoshidap,
, 
Tomohiro Nishinaq,
, 
Yoshito Komatsur,
, 
Shi R. Hans,
, 
Shinichi Shiratoris,
, 
Kohei Shitaraa,∗,'Correspondence information about the author Kohei Shitara
Open Access
DOI: https://doi.org/10.1016/j.ejca.2020.02.002
 

Highlights

  • •

    This study was conducted for gastric/gastroesophageal junction (G/GEJ) cancer.

  • •

    Efficacy and safety of S-1 + oxaliplatin (SOX) with pembrolizumab were assessed.

  • •

    Overall response rate assessed by blinded independent central review was 72.2%.

  • •

    No increase in treatment-related adverse events occurred with this combination.

  • •

    First-line SOX with pembrolizumab warrants further evaluation for G/GEJ cancer.

Abstract

Aim

The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin with pembrolizumab).

Methods

This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status.

Results

Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval 58.4–83.5) and 96.3% (95% CI 87.3–99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%).

Conclusions

SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer.

Trial registration

NCT03382600/JapicCTI-183829.

References

  1. New Global Cancer Data: Globocan 2018. https://www.uicc.org/news/new-global-cancer-data-globocan-2018.
  2. Cancer Information Service. National Cancer Center, Japan. Cancer registry and statistics (in Japanese). ; 2018
    https://ganjoho.jp/reg_stat/statistics/stat/summary.html
    October 24, 2019
  3. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017; 20: 1–19https://doi.org/10.1007/s10120-016-0622-4
  4. National Comprehensive Cancer Network. NCCN clinical practice guidelines in Oncology. (Version 2)Gastric Cancer, ; 2019
    https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
    October 24, 2019
  5. Smyth, E.C., Verheij, M., Allum, W., Cunningham, D., Cervantes, A., Arnold, D. et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 27: 38–49https://doi.org/10.1093/annonc/mdw350
  6. Muro, K., Van Cutsem, E., Narita, Y., Pentheroudakis, G., Baba, E., Li, J. et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO–ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol. 2019; 30: 19–33https://doi.org/10.1093/annonc/mdy502
  7. Bang, Y.J., Van Cutsem, E., Feyereislova, A., Chung, H.C., Shen, L., Sawaki, A. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376: 687–697https://doi.org/10.1016/S0140-6736(10)61121-X
  8. Hecht, J.R., Bang, Y.J., Qin, S.K., Chung, H.C., Xu, J.M., Park, J.O. et al. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2–positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC—a randomised phase III trial. J Clin Oncol. 2016; 34: 443–451https://doi.org/10.1200/JCO.2015.62.6598
  9. Ohtsu, A., Shah, M.A., Van Cutsem, E., Rha, S.Y., Sawaki, A., Park, S.R. et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011; 29: 3968–3976https://doi.org/10.1200/JCO.2011.36.2236
  10. Fuchs, C.S., Shitara, K., Di Bartolomeo, M., Lonardi, S., Al-Batran, S.E., Van Cutsem, E. et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019; 20: 420–435https://doi.org/10.1016/S1470-2045(18)30791-5
  11. Tabernero, J., Hoff, P.M., Shen, L., Ohtsu, A., Shah, M.A., Cheng, K. et al. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018; 19: 1372–1384https://doi.org/10.1016/S1470-2045(18)30481-9
  12. Kawazoe, A., Shitara, K., Kuboki, Y., Bando, H., Kojima, T., Yoshino, T. et al. Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer. 2019; 22: 69–76https://doi.org/10.1007/s10120-018-0843-9
  13. Wang, L., Zhang, Q., Ni, S., Tan, C., Cai, X., Huang, D. et al. Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status. Cancer Med. 2018; 7: 2612–2620https://doi.org/10.1002/cam4.1502
  14. Salem, M.E., Xiu, J., Weinberg, B.A., El-Deiry, W.S., Weiner, L.M., Gatalica, Z. et al. Characterization of tumor mutation burden (TMB) in gastrointestinal (GI) cancers. J Clin Oncol. 2017; 35: 530https://doi.org/10.1200/JCO.2017.35.4_suppl.530
  15. Bang, Y.J., Kang, Y.K., Catenacci, D.V., Muro, K., Fuchs, C.S., Geva, R. et al. Pembrolizumab alone or in combination with chemotherapy as first line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019; 22: 828–837https://doi.org/10.1007/s10120-018-00909-5
  16. Shitara, K., Özgüroğlu, M., Bang, Y.J., Di Bartolomeo, M., Mandalà, M., Ryu, M.H. et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018; 392: 123–133https://doi.org/10.1016/S0140-6736(18)31257-1
  17. Tabernero, J., Van Cutsem, E., Bang, Y.J., Fuchs, C.S., Wyrwicz, L., Lee, K.W. et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: the phase III KEYNOTE-062 study. J Clin Oncol. 2019; 37: LBA4007https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007
  18. Zitvogel, L., Galluzzi, L., Smyth, M.J., and Kroemer, G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity. 2013; 39: 74–88https://doi.org/10.1016/j.immuni.2013.06.014
  19. Hato, S.V., Khong, A., de Vries, I.J., and Lesterhuis, W.J. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin Canc Res. 2014; 20: 2831–2837https://doi.org/10.1158/1078-0432.CCR-13-3141
  20. Galluzzi, L., Senovilla, L., Zitvogel, L., and Kroemer, G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012; 11: 215–233https://doi.org/10.1038/nrd3626
  21. Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F. et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018; 378: 2078–2092https://doi.org/10.1056/NEJMoa1801005
  22. Paz-Ares, L., Luft, A., Vicente, D., Tafreshi, A., Gümüş, M., Mazières, J. et al. Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. N Engl J Med. 2018; 379: 2040–2051https://doi.org/10.1056/NEJMoa1810865
  23. Socinski, M.A., Jotte, R.M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N. et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018; 378: 2288–2301https://doi.org/10.1056/NEJMoa1716948
  24. Horn, L., Mansfield, A.S., Szczęsna, A., Havel, L., Krzakowski, M., Hochmair, M.J. et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018; 379: 2220–2229https://doi.org/10.1056/NEJMoa1809064
  25. Schmid, P., Adams, S., Rugo, H.S., Schneeweiss, A., Barrios, C.H., Iwata, H. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018; 379: 2108–2121https://doi.org/10.1056/NEJMoa1809615
  26. Rischin, D., Harrington, K.J., Grell, R., Soulieres, D., Tahara, M., de Castro, G. et al. Protocol-specified final analysis of the phase 3 KEYNOTE-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol. 2019; 37: 6000https://doi.org/10.1200/JCO.2019.37.15_suppl.6000
  27. Boku, N., Ryu, M.H., Kato, K., Chung, H.C., Minashi, K., Lee, K.W. et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol. 2019; 30: 250–258https://doi.org/10.1093/annonc/mdy540
  28. Seymour, L., Bogaerts, J., Perrone, A., Ford, R., Schwartz, L.H., Mandrekar, S. et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017; 18: e143–e152https://doi.org/10.1016/S1470-2045(17)30074-8
  29. Koizumi, W., Takiuchi, H., Yamada, Y., Boku, N., Fuse, N., Muro, K. et al. Phase II study of oxaliplatin plus S-1 as first-line treatment for advanced gastric cancer (G-SOX study). Ann Oncol. 2010; 21: 1001–1005https://doi.org/10.1093/annonc/mdp464
  30. Yamada, Y., Higuchi, K., Nishikawa, K., Gotoh, M., Fuse, N., Sugimoto, N. et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015; 26: 141–148https://doi.org/10.1093/annonc/mdu472
  31. Kito, Y., Machida, N., Kawai, S., Hamauchi, S., Tsushima, T., Todaka, A. et al. Phase II study of S-1 plus oxaliplatin 130 mg/m2 in Japanese patients with advanced gastric cancer. Int J Clin Oncol. 2018; 23: 1084–1089https://doi.org/10.1007/s10147-018-1308-1
  32. Shitara, K., Van Cutsem, E., Bang, Y.J., Fuchs, C.S., Wyrwicz, L., Lee, K.W. et al. Pembrolizumab with or without chemotherapy vs chemotherapy in patients with advanced G/GEJ cancer (GC) including outcomes according to Microsatellite Instability-High (MSI-H) status in KEYNOTE-062. (LBA44)Ann Oncol. 2019; 30https://doi.org/10.1093/annonc/mdz394.035
  33. Le, D.T., Uram, J.N., Wang, H., Bartlett, B.R., Kemberling, H., Eyring, A.D. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372: 2509–2520https://doi.org/10.1056/NEJMoa1500596
  34. Le, D.T., Durham, J.N., Smith, K.N., Wang, H., Bartlett, B.R., Aulakh, L.K. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357: 409–413https://doi.org/10.1126/science.aan6733
  35. Overman, M.J., McDermott, R., Leach, J.L., Lonardi, S., Lenz, H.J., Morse, M.A. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017; 18: 1182–1191https://doi.org/10.1016/S1470-2045(17)30422-9
  36. Overman, M.J., Lonardi, S., Wong, K.Y.M., Lenz, H.J., Gelsomino, F., Aglietta, M. et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018; 36: 773–779https://doi.org/10.1200/JCO.2017.76.9901

maagkanker, darmkanker, S-1, pembrolizumab, immuuntherapie, anti-PD medicijnen, tegafur/gimeracil/oteracil, overall overleving


Plaats een reactie ...

Reageer op "Maag en darmkanker: S-1 plus oxaliplatine samen met pembrolizumab geeft hoopvolle resultaten bij patiënten met gevorderde maag / darmkanker met 72 procent objectieve respons"


Gerelateerde artikelen