Neoadjuvant tislelizumab plus chemoradiotherapy yielded improved response rates in gastric cancer and gastroesophageal junction adenocarcinoma.
Neoadjuvant tislelizumab-jsgr (Tevimbra) plus chemoradio therapy (CRT) in patients with gastric cancer or gastroesophageal junction adenocarcinoma (GEJ) demonstrated pathologic complete response (pCR) rate and major pathologic response (MPR) rate benefits compared with CRT or chemotherapy alone, according to preliminary analysis data of the phase 2b TERRIFIC study (NCT05687357) presented at the
Among patients treated with tislelizumab and CRT (arm A; n = 35), CRT alone (arm B; n = 33), or chemotherapy alone (arm C; n = 19) in the intention-to-treat (ITT) population, the pathologic complete response (pCR) rates were 25.7%, 18.2%, and 5.3%, respectively. Among the surgery set, those who underwent a subsequent operation in arms A (n = 28), B (n = 27), and C (n = 17), the respective pCR rates were 32.1%, 22.2%, and 5.9%.
Additionally, the major pathologic response (MPR) rate in each respective arm of the ITT population was 54.3%, 48.5%, and 15.8%. In arms A, B, and C in the surgery set, the MPR rates were 67.9%, 59.3%, and 17.6%, respectively.
In arms A, B, and C in the surgery set, 32.1%, 22.2%, and 5.9% had a tumor regression grade (TRG) of 0; 32.1%, 33.3%, and 11.8% had a TRG of 1; 32.1%, 40.7%, and 41.2% had a TRG of 2, and 3.6%, 3.7%, and 41.2% had a TRG of 3. The clinical T downstaging rate was 57.1%, 63.0%, and 58.8% in each respective arm; the clinical N downstaging rate was 75.0%, 92.6%, and 70.6%.
“This is the first report of the preliminary analysis evaluating 3 neoadjuvant strategies for locally advanced gastric cancers and [GEJ adenocarcinoma],” lead study author Jia Wei, MD, PhD, of the Comprehensive Cancer Center of the Nanjing Drum Tower Hospital at Nanjing University, said in the oral presentation. “Our results show that the combination with the PD-1 [inhibitor] and CRT have a higher pCR rate when compared with CRT or chemotherapy alone.”
In arms A, B, and C, the most common surgical method delivered was total gastrectomy, occurring in 78.6%, 77.8%, and 64.7% of each cohort. The median number of lymph nodes examined was 23.5 (range, 0-58), 21 (range, 14-41), and 30 (range, 15-89) in the respective arms. The R0 resection rate was 100% across all arms.
Patients 18 years and older with histologically confirmed locally advanced gastric cancer or adenocarcinoma of the GEJ, AJCC stage III to IVa disease, and an ECOG performance status of 0 or 1 were randomly assigned in a 2:2:1 ratio to receive tislelizumab plus CRT, CRT alone, or chemotherapy alone.
In arm A, patients received 200 mg of intravenous tislelizumab on day 1 of cycle 1, days 1 and 22 of cycle 2, and day 1 of cycle 3 during neoadjuvant treatment as well as adjuvant tislelizumab every 3 weeks. CRT was given at 45 Gy via volumetric modulated arc therapy (VMAT) or Tomotherapy, and chemotherapy consisted of S-1 and oxaliplatin (SOX) or S-1 plus nab-paclitaxel for 3 cycles during neoadjuvant therapy. During adjuvant therapy, S-1 was given at maintenance for 3 cycles.
The median age in arms A, B, and C were 63.0 years (range, 43.0-75.0), 61.0 years (range, 47.0-76.0), and 62.0 years (range, 47.0-74.0). Most patients had an ECOG performance status of 2 (65.7%, 66.7%, and 57.9%), tumors located in the stomach (62.9%, 63.6%, and 63.2%), and TNM stage III disease (65.7%, 63.6%, and 68.4%). Additionally, 62.9%, 54.6% and 42.1% had T4a disease, 71.4%, 69.7%, and 63.2% had N2 disease, and 54.3%, 54.6%, and 52.6% had an intestinal Lauren subtype. The most common chemotherapy regimen was S-1 plus nab-paclitaxel (68.6%, 78.8%, and 68.4%); in arms A and B, the median radiotherapy dose was 41.4 (range, 28.8-45.0) and 45.0 (range, 39.6-50.0).
The primary end point of the trial was pCR rate in the ITT population. Secondary end points included pCR in the surgery set, MPR in the ITT population and the surgery set, objective response rate, disease control rate, safety, and 2-year event-free survival and overall survival rates.
Treatment-related adverse effects (TRAEs) of any grade occurred in 77.1% of arm A, 75.8% of arm B, and 57.9% of arm C. The incidence of grade 3 or higher TRAEs in each respective arm was 31.4%, 24.2%, and 15.8%. TRAEs leading to chemotherapy discontinuation occurred in 2.9%, 3.0%, and 0% of the respective arms.
In arms A and B, TRAEs leading to radiotherapy discontinuation occurred in 8.6% and 3.0% of the respective arms, 5.7% of which were due to grade 3 or higher TRAEs in arm A. Furthermore, TRAEs leading to immunotherapy discontinuation occurred in 5.7% of arm A, both of which were grade 3 or higher, and 28.6% of this cohort experienced immune-related AEs, 2.9% of which were grade 3 or higher.
“[Adverse] effects are manageable and the survival data are still ongoing. Also, we [will be] doing a biomarker analysis in the future,” Wei concluded.
Wei had no relationships to disclose.
