General survival (OS) and progression-free survival (PFS) outcomes with tislelizumab (Tizveni) plus chemotherapy, as outlined by Tumor Space Positivity (TAP) rating and mixed constructive rating (CPS), had been comparable at matched PD-L1 positivity thresholds, suggesting that each TAP rating and CPS are viable measurements of PD-L1 expression in gastric most cancers/gastroesophageal junction (GEJ) most cancers.1
Findings from a post-hoc evaluation of the section 3 RATIONALE-305 trial (NCT03777657) offered on the 2024 ESMO Gastrointestinal Cancers Congress confirmed that TAP rating and CPS at matched thresholds of 10% or higher, 1% or higher, and 5% or higher displayed notable concordance amongst sufferers enrolled in RATIONALE-305. Furthermore, enhancements in OS and PFS with tislelizumab plus chemotherapy in line with TAP rating and CPS had been just like beforehand reported leads to sufferers with a PD-L1 TAP rating of 5% or higher.
The median OS for sufferers with a TAP rating of 1% or higher, 5% or higher, and 10% or higher was 15.0 months (95% CI, 13.3-16.7), 16.4 months (95% CI, 13.6-19.1), and 22.5 months (95% CI, 16.4-26.4) with the tislelizumab mixture; corresponding median OS outcomes within the placebo arm had been 12.8 (95% CI, 12.1-14.1), 12.8 (95% CI, 12.0-14.5), and 12.3 (95% CI, 11.3-14.9). This translated to HRs of 0.78 (95% CI, 0.67-0.90), 0.72 (95% CI, 0.59-0.88), and 0.57 (95% CI, 0.43-0.76).
For sufferers with a CPS of 1 or higher, 5 or higher, and 10 or higher, the median OS within the experimental arm was 15.1 months (95% CI, 13.6-17.2), 17.8 months (95% CI, 14.8-20.8), and 18.0 months (95% CI, 13.6-23.2). Within the placebo arm, respective median OS outcomes had been 12.9 months (95% CI, 12.1-14.1), 13.2 months (95% CI, 12.1-12.6), and 12.9 months (95% CI, 11.5-15.5). This translated to HRs of 0.78 (95% CI, 0.67-0.91), 0.73 (95% CI, 0.60-0.89), and 0.68 (95% CI, 0.52-0.90).
“These PD-L1 subgroup outcomes, together with earlier outcomes from the RATIONALE-305 main evaluation in all randomized sufferers, assist tislelizumab plus chemotherapy as a brand new first-line remedy possibility for superior HER2-negative gastric most cancers/GEJ most cancers,” Markus Moehler, MD, PhD, head of Gastrointestinal Oncology on the Mainz College Clinic in Germany, acknowledged in a presentation of the info.
Relating to PFS, sufferers with a TAP rating of 1% or higher, 5% or higher, and 10% or higher had HRs of 0.78 (95% CI, 0.67-0.91), 0.69 (95% CI, 0.57-0.84), and 0.56 (95% CI, 0.42-0.74); respective PFS HRs for a CPS of 1 or higher, 5 or higher, and 10 or higher had been 0.77 (95% CI, 0.66-0.90), 0.73 (95% CI, 0.60-0.90), 0.69 (95% CI, 0.53-0.91).
“Tislelizumab added to chemotherapy as first-line remedy for gastric most cancers/GEJ most cancers improved PFS in sufferers with PD-L1 TAP scores of 10% or higher and 1% or higher,” Moehler acknowledged.
The PD-L1 TAP rating evaluates each immune and tumor cells for superior gastric/GEJ most cancers and was each analytically developed and validated within the RATIONALE-305 examine. Beforehand reported knowledge from this examine demonstrated a major OS profit with first-line tislelizumab plus chemotherapy vs chemotherapy alone in all sufferers, together with these with a TAP rating of 5% or higher (HR, 0.71; 95% CI, 0.58-0.86).2
RATIONALE-305 enrolled sufferers with histologically confirmed gastric or GEJ most cancers who had not beforehand acquired remedy for unresectable, regionally superior or metastatic illness and whose tumors didn’t show HER2 positivity.
Upon enrollment, sufferers had been randomly assigned 1:1 to obtain 200 mg of intravenous tislelizumab each 3 weeks with chemotherapy or placebo with chemotherapy. Chemotherapy regimens consisted of oxaliplatin at 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice each day for days 1 to 14 each 3 weeks or cisplatin at 80 mg/m2 on day 1 plus 5-fluororacil at 800 mg/m2 each day on days 1 to five each 3 weeks. Upkeep remedy was administered till unacceptable toxicity or progressive illness.
Sufferers had been stratified in line with area of enrollment, PD-L1 rating (5% or higher vs lower than 5%), the presence or absence of peritoneal metastasis, and investigator’s selection of chemotherapy routine.
The first finish factors of the evaluation had been OS within the PD-L1–constructive inhabitants (PD-L1 TAP rating of 5% or higher) and intention-to-treat populations. Key secondary finish factors comprised of subgroup evaluation of OS and PFS using exploratory PD-L1 TAP rating and CPS, in addition to TAP rating vs CPS concordance.
TAP rating was calculated by assessing the area occupied by PD-L1 staining tumor and immune cells in a given tumor space and was scored by visual-based estimation. CPS was outlined because the variety of PD-L1 staining tumor and immune cells out of the whole variety of viable tumor cells and was scored by cell rely.
Of the randomized sufferers (n = 997), all had an evaluable TAP rating, whereas 974 had evaluable post-hoc CPS outcomes. Amongst these with an evaluable TAP rating (tislelizumab arm, n = 501; placebo arm, n = 496), sufferers had a PD-L1 standing TAP rating of 1% or higher (86.2%; 91.3%), lower than 1% (13.8%; 8.7%), 5% or higher (54.7%; 54.8%), lower than 5% (45.3%; 45.2%), 10% or higher (27.1%; 29.2%), and fewer than 10% (72.9%; 70.8%).
Amongst members with an evaluable CPS rating, sufferers had a rating of 1 or higher (tislelizumab arm, 85.5%; placebo arm, 89.9%), lower than 1 (14.5%; 10.1%), 5 or higher (51.7%; 55.7%), lower than 5 (48.3%; 44.3%), 10 or higher (30.8%; 28.6%), and fewer than 10 (69.2%; 71.4%).
“Prevalence was comparable throughout arms by TAP rating or CPS beneath totally different thresholds,” Moehler reported within the presentation.
Within the remaining sufferers with TAP scores of lower than 10%, lower than 5%, and fewer than 1%, unstratified HRs for OS had been 0.91 (95% CI, 0.77-1.07), 0.91 (95% CI, 0.74-1.12), and 0.98 (95% CI, 0.64-1.50), respectively. For sufferers with CPS at matched thresholds, unstratified HRs for OS had been 0.87 (95% CI, 0.73-1.03), 0.89 (95% CI, 0.72- 1.09), and 1.01 (95% CI, 0.66-1.52), respectively.
Unstratified PFS HRs for sufferers in these 3 PD-L1 subgroups in line with TAP rating, respectively, had been 0.90 (95% CI, 0.76-1.06), 0.92 (95% CI, 0.75-1.14), and 0.87 (95% CI, 0.54-1.41). Sufferers in at matched thresholds by CPS had PFS HRs of 0.82 (95% CI, 0.69-0.97), 0.82 (95% CI, 0.67-1.02), and 0.80 (95% CI, 0.52-1.23).
Appreciable correlation was noticed between the TAP rating and CPS in superior gastric/GEJ most cancers, with an interclass correlation coefficient (ICC) of 0.81 (95% CI, 0.79, 0.83). The TAP rating and CPS confirmed concordance by way of total p.c settlement (OPA) and Cohen’s Kappa at matched thresholds for every rating. The OPA was 95% (95% CI, 94%-97%) on the 1% threshold, 82% (95% CI, 80%-85%) on the 5% threshold, and 85% (95% CI, 83%-87%) on the 10% threshold, respectively.
Disclosures: Professor Moehler experiences serving in a consultancy/advisory function for Bayer, Merck Sharp & Dohme (MSD), Merck Serono, Amgen, Taiho Pharmaceutical, Pfizer, Roche, Lilly, Servier Laboratories, BeiGene, Bristol Myers Squibb (BMS), AstraZeneca, Astellas, Dragonfly, and Novartis; receiving honoraria from Amgen, Roche/Genentech, Merck Serono, MSD Oncology, BMS, AstraZeneca/MedImmune, Servier Laboratories, Pierre Fabre, Sanofi, Falk Basis, Transcenta Holding, Daiichi Sankyo, Astellas Pharma, and Nordic Pharma; receiving grant/analysis funding from Amgen, Leap Therapeutics, Merck Serono, and MSD; different remuneration from Amgen, Merck Serono, Roche, Bayer, American Society for Scientific Oncology (ASCO), German Most cancers Society, MSD, European Society for Medical Oncology (ESMO), BeiGene, and the European Organisation for Analysis and Remedy (EORTC).
References
- Moehler M, Oh D, Kato Ok, et al. Tislelizumab (TIS) plus chemotherapy (CT) vs placebo (PBO) plus CT in HER2-negative superior or metastatic gastric or gastro-esophageal junction adenocarcinoma (GC/GEJC): PD-L1 biomarker evaluation from RATIONALE-305. Ann Oncol. 2024;35(suppl 1):S162-S204.Doi: 10.1016/annonc/annonc1482
- Qiu MZ, Oh DY, Kato Ok, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line remedy for superior gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, section 3 trial. BMJ. 2024;385:e078876. Printed 2024 Could 28. doi:10.1136/bmj-2023-078876
