Laura A. Dawson, MD, on Hepatocellular Carcinoma: Phase III Data on Sorafenib vs Stereotactic Body Radiation Therapy
2023 ASCO Gastrointestinal Cancers Symposium
Laura A. Dawson, MD, of Canada’s Princess Margaret Cancer Centre, discusses phase III findings from the NRG/RTOG1112 study, which showed that stereotactic body radiation therapy (SBRT) administered prior to sorafenib vs sorafenib alone, improved outcomes in patients with advanced hepatocellular carcinoma. SBRT may become a new standard treatment option for patients with locally advanced disease, especially in the presence of macrovascular invasion (Abstract 489).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The purpose of the randomized Phase 3 study, NRG/RTOG1112, was to determine the benefits of SBRT in the setting of locally advanced hepatocellular carcinoma. The background is that patients with locally advanced disease, who are unsuitable for standard local or regional therapies, have been treated with systemic therapy. And those who have invasion of their cancer into the large hepatic vessels are particularly challenging to treat.
External beam radiation has been used in single-arm studies and had shown some benefit, but there has not been a Phase 3 study asking the question of whether external beam radiation can improve survival. And so the randomized Phase 3 study, RTOG1112, asked the question, does SBRT improve survival in these patients compared to sorafenib alone? And that was the standard of care systemic therapy at the study inception.
In this study, patients with very advanced cancer were eligible, up to 20 centimeters of tumor in the liver, any degree of vascular invasion. They had to be suitable for sorafenib, and it was a one-to-one randomized study with 193 patients randomized. The study was stopped early due to a change in the systemic standard of care from sorafenib to immunotherapy-based, and thus the power was reduced from 80% to 65% with the lower sample size. Despite the reduced power due to the smaller sample size than anticipated, clinically important and statistically significant improvement in outcomes were seen with the addition of SBRT to sorafenib alone. The median's survival improved from 12,3 months to 15,8 months with the addition of SBRT to sorafenib. And similarly, there is a near doubling of median time to progression and progression-free survival with the addition of SBRT compared to sorafenib alone.And on multi-variable analyses, statistically significant and important improvements in overall survival were seen with the addition of SBRT.
Furthermore, there was a trend to improved quality of life in patients who received SBRT. The FACT-Hep was used. And at six months following treatment, a larger proportion of patients treated with SBRT reported clinically important improvement in quality of life, approximately 35%, versus 10% of patients who received sorafenib alone. There is no concerning increase in adverse events in patients treated with SBRT, and overall, the treatment was well tolerated. Most of the adverse events are likely due to the underlying liver disease that can lead to sequelae and liver failure. 75% of the patients treated on this trial had macrovascular invasion, and most of those patients had invasion of their tumor to the main portal vein, and right or left main portal vein, and are at high risk of having decline in liver function due to their very locally advanced cancer. So effective therapies, such as SBRT that can help control that, can hopefully allow patients to have less adverse events, and then improve quality of life and survival as we saw in this trial.
Next steps would be to consider what the role of SBRT is in the immunotherapy era. So similar randomized studies of atezolizumab and bevacizumab, plus or minus SBRT, are in development, and hopefully will answer that question.
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).
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).
Josep Tabernero, MD, PhD, of Spain’s Vall d’Hebron Institute of Oncology, discusses phase III findings from the SUNLIGHT study, which showed that trifluridine and tipiracil (FTD/TPI) plus bevacizumab resulted in improved outcomes compared with FTD/TPI alone in patients with refractory metastatic colorectal cancer. Improvements in survival occurred irrespective of tumor sidedness, RAS mutational status, and receipt of prior bevacizumab. This three-drug regimen may represent a new standard of care for patients whose cancer has progressed after two lines of therapy (Abstract 4).
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.
Zev A. Wainberg, MD, of the UCLA School of Medicine, discusses phase III findings from the NAPOLI-3 trial, which showed that first-line NALIRIFOX (liposomal irinotecan plus fluorouracil/leucovorin plus oxaliplatin) improved overall and progression-free survival compared with nab-paclitaxel plus gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma. The safety profile of NALIRIFOX was manageable and consistent with the profiles of each agent (Abstract LBA661).