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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

Kohei Shitaraa,∗,'Correspondence information about the author Kohei Shitara
Open Access

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.

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