Samuel Cytryn, MD, and David B. Zhen, MD, discuss how immunotherapy plus chemotherapy has improved the durability of outcomes in advanced GI cancers.

Immunotherapy's Role in Improving Durability of Outcomes in Advanced Upper GI Cancers

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Samuel Cytryn, MD, and David B. Zhen, MD, on factors for selecting nivolumab plus chemotherapy or ipilimumab in esophageal squamous cell carcinoma.

Factors for Selecting Nivolumab Plus Chemo or Nivolumab Plus Ipilimumab in Advanced ESCC

Samuel Cytryn, MD, and David B. Zhen, MD, on long-term data for nivolumab plus chemotherapy or ipilimumab in advanced esophageal squamous cell carcinoma.

Long-Term Data for Frontline Nivolumab Plus Chemo or Ipilimumab in Advanced ESCC

Samuel Cytryn, MD, and David B. Zhen, MD, discuss findings from a Q-TWiST analysis of the CheckMate 649 trial in advanced gastric/GEJ cancer.

A Q-TWiST Analysis from the CheckMate 649 Trial of Nivolumab/Chemo in Advanced Gastric/GEJ Cancer

Samuel Cytryn, MD, and David B. Zhen, MD, on 4-year data from CheckMate 649 for nivolumab plus chemotherapy in first-line advanced gastric/GEJ cancer.

4-Year Data for First-Line Nivolumab Plus Chemo in Advanced Gastric/GEJ Cancer

Samuel Cytryn, MD, and David B. Zhen, MD, discuss how immunotherapy has affected the treatment paradigm for upper gastrointestinal cancers.

Immunotherapy's Effect on the Upper GI Cancer Treatment Paradigm

David Zhen, MD, physician, Fred Hutchinson Cancer Center, assistant professor, the University of Washington School of Medicine, assistant professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses future research efforts in poorly differentiated small cell neuroendocrine carcinomas.

The randomized phase 2/3 SWOG S2012 trial (NCT05058651) is evaluating the addition of atezolizumab (Tecentriq) to the standard-of-care chemotherapy for patients with metastatic small cell neuroendocrine carcinomas that originate outside the lung.

Though neuroendocrine tumors tend to be less aggressive, with patients achieving survival measured in years, poorly differentiated neuroendocrine carcinomas represent a subset of these cancers, Zhen says. These rare tumors are typically much more aggressive than other neuroendocrine tumors, Zhen explains.

Under the current standard of care, with neuroendocrine carcinomas could survive for 1 year or less, and there is a need develop improved therapies for this subset of patients, Zhen concludes.

David Zhen, MD, discusses future research efforts in poorly differentiated small cell neuroendocrine carcinomas.


Dr. Zhen on Future Research Efforts in Neuroendocrine Carcinomas

David Zhen, MD, assistant professor, University of Washington School of Medicine, assistant professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, physician, Seattle Cancer Care Alliance, discusses the need for novel therapies in poorly differentiated small-cell-type neuroendocrine tumors (NETs).

Limited therapeutic progress has been made in poorly differentiated small-cell-type NETs, Zhen says. Historically, the treatment paradigm has been based on experience with other small-cell-type diseases, such as small cell lung cancer. As such, platinum/etoposide chemotherapy has remained the standard of care for patients with poorly differentiated small-cell-type NETs but provides modest responses. The median progression-free survival is between 4 and 6 months and overall survival is often less than 1 year, Zhen adds.

To improve upon the limited responses noted with platinum/etoposide, an ongoing phase 2/3 clinical trial (NCT05058651) is evaluating platinum/etoposide with or without atezolizumab (Tecentriq) in patients with poorly differentiated extrapulmonary small cell NETs, Zhen concludes. 

David Zhen, MD, discusses the need for novel therapies in poorly differentiated small-cell-type neuroendocrine tumors.



Dr. Zhen on the Need for Novel Therapies in Poorly Differentiated Small-Cell-Type NETs 

David Zhen, MD, assistant professor, University of Washington School of Medicine, assistant professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, physician, Seattle Cancer Care Alliance, discusses advancements in the treatment of patients with gastroenteropancreatic neuroendocrine tumors.

Treatments for this patient population have been limited, thus far, with somatostatin analogs, such as octreotide (Sandostatin) and lanreotide (Somatuline), as well as some chemotherapy agents serving as the foundation, according to Zhen. Advancements were made with the advent of peptide receptor radionuclide therapy with lutetium Lu 177 dotatate (177Lu-Dotatate; Lutathera), as well as sunitinib (Sutent), which has been FDA approved for the treatment of pancreatic neuroendocrine tumors, Zhen says. However, once patients progress on these therapies, there are very few other treatment options available, Zhen notes.

Recent data have shown that surufatinib demonstrated an improved progression-free survival vs placebo in previously treated patients with both extra-pancreatic and pancreatic neuroendocrine tumors, Zhen explains. The drug has been approved for use in China, and a 

new drug application was accepted by the FDA in July 2021

Furthermore, preliminary data from ongoing studies has suggested benefit with cabozantinib (Cabometyx) plus lenvatinib (Lenvima) for the treatment of this patient population, Zhen adds. The data with this combination have been impressive because they demonstrate efficacy, even if patients have already been exposed to other TKIs. The mechanism of action of these agents target pathways other than VEGF, and therefore can potentially overcome resistance, Zhen concludes.

David Zhen, MD, discusses advancements in the treatment of patients with gastroenteropancreatic neuroendocrine tumors.

David B. Zhen, MD

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