Filippo Pietrantonio, MD, on Gastric or Gastroesophageal Junction Adenocarcinoma: Recent Data on Treatment With Tremelimumab and Durvalumab
2023 ASCO Gastrointestinal Cancers Symposium
Filippo Pietrantonio, MD, of Italy’s Istituto Nazionale dei Tumori, discusses phase II results from the INFINITY trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability–high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). These results open the way to investigate nonoperative management in patients with clinical, pathologic, and molecular complete response after T300/D (300 mg of tremelimumab and 1,500 mg every 4 weeks of durvalumab) (Abstract 358).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Microsatellite instability is associated with better survival and potential lack of benefit from chemotherapy in patients with the resectable gastric cardiac junction cancer, and it is one of the strongest predictors of the efficacy of immunotherapy. In early stage disease, the activity of immunotherapy is even higher, and immune checkpoint inhibitors may allow the emission of chemotherapy, radiotherapy, or even surgery. Finally, a single high dose of tremelimumab added to the anti PD-L1 agent durvalumab may induce higher T cell expansion and is approved for the treatment of patients with HCC.
The INFINITY trial enrolled patients with MSI-high and deficient mismatch repair, resectable gastric cardiac junction cancer and clinical stage T2 or higher. Patients were treated with a single high dose of tremelimumab and 300 milligrams, plus three cycles of durvalumab every four weeks at standard doses. After re-staging, patients in cohort one, the court was presented at the meeting, received surgery and standard follow up.
The results of cohort one have been evaluated by an independent data monitoring committee, and so now the recruitment in cohort two of the trial has started to evaluate the same regimen as non-operative management strategy. The primary point of the first cohort was pathological complete response, and 18 patients were enrolled. Regarding baseline characteristics, the median was very high, 71 years old, consistent with these molecular subgroups, and 40% of the patients had T4 tumors. Regarding the primary endpoint, among resected patients, most of had pathological down staging. So, among all evaluable patients, the PCR rate was 60%. Also, the rate of major to complete pathological response was 80%.
The treatment was well tolerated, so no unexpected immune-related adverse events occurred, and grade 3 or more toxicities had very low frequency and did not impair the feasibility of surgery. We did, also, subgroup analysis and noted that the PCR rate was very low in the T4 stage subgroup.
Basically, what we learned from this trial, from cohort one of this trial, that T300/D regimen, or the so-called stride regimen, is safe in this population and has promising eradicating activity in patients with MSI-high resectable gastric cancer. We also know that larger studies are needed, but immunotherapy will soon represent the standard of care for this molecular subgroup of patients. And of course, we still have to investigate the optimal combinations of immune checkpoint inhibitors, the proper treatment duration, and the goal of treatment, whether it is neoadjuvant or organ preservation. In fact, the recruitment in cohort two of INFINITY trial is now ongoing after the EDMC evaluation and amendment of the protocol to exclude the T4 tumors from non-operative management. The INFINITY study was sponsored by the GONO Foundation in Italy, which is a nonprofit organization dedicated to the design of clinical trials.
Rachna T. Shroff, MD, of the University of Arizona Cancer Center, discusses phase III results from the SWOG 1815 study, which compared gemcitabine, cisplatin, and nab-paclitaxel vs gemcitabine and cisplatin in patients with newly diagnosed, advanced biliary tract cancers. Although adding nab-paclitaxel to gemcitabine and cisplatin did not improve median overall survival in this population, exploratory analyses in patients with locally advanced disease or gallbladder cancer suggest potential clinical utility in these settings, which may warrant further evaluation (Abstract LBA490).
Souya Nunobe, MD, PhD, of Japan’s Cancer Institute Hospital and the Japanese Foundation for Cancer Research, discusses 5-year follow-up results of the phase III OPAS-1 trial, which compared four and eight courses of S-1, a novel oral fluoropyrimidine derivative adjuvant chemotherapy for patients with stage II gastric cancer. These final follow-up findings confirmed the benefit of S-1 and its use for 1 year to treat this population (Abstract 381).
Richard S. Finn, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, discusses findings from the RATIONALE-301 study, which showed that patients with unresectable hepatocellular carcinoma (HCC) treated with first-line tislelizumab had better health-related quality-of-life outcomes compared with those treated with sorafenib, particularly in terms of fatigue and physical functioning. These results, along with the effects on overall survival, response rate, and a favorable safety profile, support the benefit of tislelizumab as a potential first-line treatment option in this patient population (Abstract 495).
Manik A. Amin, MD, of Dartmouth Cancer Center, discusses the future of immunotherapy in gastrointestinal cancers, the challenges of creating effective adoptive cell therapies, and the next generation of immune checkpoint inhibitors.
Laura A. Dawson, MD, of Canada’s Princess Margaret Cancer Centre, discusses phase III findings showing that compared with best supportive care alone, single-fraction whole-liver radiation therapy appears to improve hepatic pain in the majority of patients with treatment-refractory or -ineligible hepatocellular carcinoma or liver metastases. In addition, the data indicated a trend for improved 3-month survival with radiation therapy (Abstract LBA492).