Steven Maron, MD, MSc, medical oncologist, Gastrointestinal Malignancies, Esophageal and Gastric Cancers, Targeted Therapies, Memorial Sloan Kettering Cancer Center, discusses the role of PD-1 inhibition in esophagogastric cancer.

After previously receiving FDA approvals for third-line treatment in esophagogastric cancer, pembrolizumab (Keytruda) and nivolumab (Opdivo) have both been approved in the first-line setting for metastatic disease; however, guidelines for the use of these agents remain murky,based on PD-L1 and mismatch repair status, Maron says. Additionally, adjuvant nivolumab has been approved for the treatment of patients with esophageal or gastroesophageal junction cancer who have received chemoradiotherapy followed by surgery, based on data from the phase 3 CheckMate-577 trial (NCT027434940), Maron explains.

Patients with gastric cancers tend to benefit more from PD-1–directed therapies than those with esophageal cancers, Maron continues. Additionally, patients with squamous cell cancers also receive a greater benefit from PD-1 inhibition, since patients with adenocarcinomas generally have low PD-L1 scores, Maron adds. Notably, current approvals exclude patients who receive perioperative chemotherapy who tend to have high PD-L1 scores and are more likely to be microsatellite instable, which is a considerable gap in esophagogastric cancer, Maron concludes.

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Steven Maron, MD, MSc, discusses the role of PD-1 inhibition in esophagogastric cancer.


Dr. Maron on the Role of PD-1 Inhibition in Esophagogastric Cancer

Steven Maron, MD, MSc, medical oncologist, Gastrointestinal Malignancies, Esophageal and Gastric Cancers, Targeted Therapies, Memorial Sloan Kettering Cancer Center, discusses sequencing considerations in the frontline treatment of gastrointestinal (GI) cancers.

Two retrospective publications from Japan and Minnesota, respectively, examined the sequencing oframucirumab (Cyramza)-based therapy following immunotherapy with a PD-1 inhibitor, Maron says. These studies found a dramatic increase in response rates in these patients, Maron adds. However, the durability of these responses is unknown, and this sequencing of treatments has yet to demonstrate a benefit in progression-free survival or overall survival, Maron explains.

However, the response benefit alone lends credence to the idea of using ramucirumab in the second line after first-line PD-1 inhibition, Maron continues. Additionally, there are concerns about patients who are PD-L1–low or PD-L1–negative not benefiting from first-line PD-1 inhibition, adding more questions to the sequencing options for these patients, Maron concludes.

Steven Maron, MD, MSc, discusses sequencing considerations in the frontline treatment of gastrointestinal cancers.


Dr. Maron on Sequencing Considerations in the Frontline Treatment of GI Cancers

Steven Maron, MD, MSc, medical oncologist, Gastrointestinal Malignancies, Esophageal and Gastric Cancers, Targeted Therapies, Memorial Sloan Kettering Cancer Center, discusses 

-positive tumors in esophageal gastric cancers.

-postive tumors are the same, as some are more heterogeneous, with 

 positivity between 5% and 50%, and some are homogeneous and more HER2-positive, Maron says. Patients with stronger 

expression typically have better outcomes, Maron adds.

-positive tumors due to a resistance mechanism that is present at the onset of disease, Maron adds. Approximately one-third of patients no longer have 

 expression after receiving HER2-directed therapy, Maron explains. When the remaining patients experience disease progression or recurrence, an escape mechanism is present in the form of another mutation, such as 

Current strategies involve exploring ways handle these resistance mechanisms, rather than using alternative HER2 inhibitors, Maron continues. Antibody-drug conjugates are being used to deliver chemotherapy or radiation with 

 expression used more as a locator to deliver the treatment payload, Maron concludes.

Steven Maron, MD, MSc, discusses HER2-positive tumors in esophageal gastric cancers.


Steven Maron, MD, MSS

Articles

Dr. Maron on the Role of PD-1 Inhibition in Esophagogastric Cancer

Dr. Maron on Sequencing Considerations in the Frontline Treatment of GI Cancers

Dr. Maron on HER2-Positive Tumors in Esophageal Gastric Cancers