Adding Immunotherapy to Perioperative Chemotherapy For Gastroesophageal Cancer Beneficial

In an interview with Targeted Oncology, Thierry Alcindor, MD, discusses the benefits of adding avelumab to perioperative chemotherapy for the treatment of gastroesophageal cancer in greater detail.

Perioperative chemotherapy can improve cure rates in locally advanced gastroesophageal adenocarcinoma. Adding the immune checkpoint inhibitor avelumab to perioperative chemotherapy may help to further increase cure rates.1

During a single-arm, open label, single-group assignment study with an estimated enrollment of 55 participants, avelumab was added to perioperative chemotherapy. In total, 4 cycles were administered to patients. The primary end point of the study is pathologic complete response. Secondary end points include 2-year disease free survival and safety.2

A preliminary analysis of 28 patients found adding avelumab to chemotherapy was safe and effective. Grade 3 stomatitis occurred in 2/28 patients, nausea 2/28 patients, and vomiting in 1/28 patients. At the median follow-up of 1.5 years, the disease-free survival at 12 months is projected to be 0.92 (95% CI 0.83-1.00) and 0.77 at 24 months (95% CI 0.58-1.00).

In an interview with Targeted Oncology, Thierry Alcindor, MD, an investigator at the Cancer Research Program at the McGill University Health Centre, discusses the benefits of adding avelumab to perioperative chemotherapy for the treatment of gastroesophageal cancer in greater detail.

TARGETED ONCOLOGY: Can you give me an overview of your article, Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma?

ALCINDOR: Basically, perioperative chemotherapy, as we call it, improves the cure rate of patients when added to surgery, patients with gastroesophageal cancer. However, even with the best-case scenario, a little less than 50% of patients are cured. So, there is room for improvement. And what we have done in that trial was to see whether there was any hint of better activity when immunotherapy with the drug called avelumab, was added to a chemotherapy backbone. So, this is an investigator-initiated trial that we are conducting at the McGill University Health Center. These are preliminary results. And those results are based on what we call a surrogate endpoint, which is pathologic complete response. So, that tells us how effective this treatment is at killing tumor cells in the tumor itself. So, our results are encouraging in that when we look at the number of patients who have had a complete or near complete pathologic response, it seems to be better than what we have seen in patients who have received chemotherapy only. Again, preliminary results. The study is not completed yet. And hopefully in a year from now, we'll have more complete data to the present.

Can you go into study design and what your primary endpoints were?

Pathologic complete response is the absence of any visible tumor cell when the tumor has been removed surgically, after preoperative treatment. So, the pathologic complete response rate in many publications with chemotherapy only has been described as ranging between 7% and 15%. And that includes both complete and near complete responses. In our study, on 28 patients, we have found that 6 patients, so 22%, had a complete or near complete response, something that we find encouraging, although we acknowledge that this is an interim analysis. And to answer maybe another question. Some studies suggest that patients who have a complete or near complete response fare better than those without.

Have any of these results been particularly significant?

I would say in all honesty, that we're encouraged by these results, but we don't find that they are conclusive yet. Twenty-eight patients are not enough to conclude on, but is this combination worthy of further examination of avelumab and chemotherapy? I believe so. We plan to do additional molecular studies to try to see whether some groups of patients would be more likely to respond. Our goal is to have approximately 50 patients enrolled, so that we have a larger number of patients to recall them.

Why was this specific combination chosen?

Chemotherapy regimens that contain 3 drugs are clearly more active than those that have 2. Our group published several years ago, very good results with a regimen called DCF. The only problem with that regimen was that it was relatively toxic. So, we have used a modified version of that regimen and added avelumab, the immunotherapy drug, to it with the hope that there will be synergy or benefit with a similar combination. The drug called docetaxel, is believed to be the one that's particularly responsible for the success of FLOT, which is considered the reference chemotherapy combination outside of clinical trials.

REFERENCES:
1.Alcindor, T, Opu T, Elkrief A, et al. Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results. Jour Clinc Oncl. 2021;39(155)
2.mDCF + Avelumab in Resectable Esophago-gastric Adenocarcinoma (EGA). ClinicalTrials.gov. Accessed August 12, 2021. https://bit.ly/2VIZRbm.