Tislelizumab + chemo exhibits favourable tolerability for gastric cancer, oesophageal SCC
The addition of the investigational, humanized IgG4* monoclonal antibody tislelizumab to chemotherapy was generally well-tolerated and generated favourable antitumour activity in patients with advanced gastric/gastroesophageal (G/GEJ) cancer and oesophageal squamous cell carcinoma (SCC), according to data presented at ASCO GI 2019.
Fifteen Chinese participants (median age 59 years, 73 percent male) with histologically or cytologically confirmed HER2**-negative G/GEJ received intravenous (IV) tislelizumab 200 mg, oxaliplatin 130 mg/m² (up to six cycles), and capecitabine 1,000 mg/m² (twice/day; days 1–14). The regimen was administered every 3 weeks (Q3W). Tumour responses were evaluated every 9 weeks in the first year and every 12 weeks thereafter. [ASCO GI 2019, abstract 11]
The most frequent treatment-related adverse event (AE) was asthenia (53 percent), followed by increased aspartate aminotransferase (AST) and nausea (47 percent each), and increased alanine aminotransferase (ALT) and vomiting (40 percent each). Three patients discontinued treatment due to ascites, increased ALT/AST, or elevated total bilirubin. No fatal AEs occurred.
“[The] reported AEs were consistent with the known tolerability profile of [programmed cell death-1] inhibitors in combination with chemotherapy,” said the researchers, adding that the AEs were mostly mild to moderate in severity.
After a median follow-up of 181 days, 47 percent had confirmed partial response while 20 percent had stable disease. Objective response and disease control rates were 47 percent and 80 percent, respectively, translating to favourable antitumour activity, noted the researchers.
In a subanalysis of the same study, 15 participants (median age 61 years, 93 percent male) with inoperable, locally advanced oesophageal SCC received IV tislelizumab 200 mg, cisplatin 80 mg/m² (up to six cycles), and fluorouracil 800 mg/m²/day (up to six cycles; days 1–5) Q3W. [ASCO GI 2019, abstract 14]
Decreased appetite was the most common AE (n=9) followed by nausea, anaemia, and reduction in white blood cell count (n=8, 6, and 6, respectively). One patient experienced grade 5 hepatic dysfunction which, according to the researchers, could be treatment-related. Four patients discontinued treatment due to AEs (grade 3 tracheal fistula, grade 3 lung infection, grade 2 pneumonitis, and grade 3 increase in AST).
These findings highlight the potential of tislelizumab as a therapeutic option for G/GEJ cancer which currently has limited treatment options, with chemotherapy primarily used for unresectable, metastatic HER2-negative cases, noted the researchers. [Lancet 2016;388:2654-2664; World J Gastroenterol 2016;22:4812-4823] “[Taken together,] the safety, tolerability, and antitumour activity observed in this study support continued development of tislelizumab in [this setting],” said the researchers.