Johanna Bendell, MD: In Japan, there are screening protocols that catch these cancers early so they can be cured before they get to an advanced setting. Here in the United States, we don’t have that so much. How are we trying to work to look at earlier diagnosis or education around symptoms for these patients?
Daniel Catenacci, MD: That’s a good question. Just to reiterate what’s been said so far, the way I think about it, there’s 3 diseases: esophageal squam, gastroesophageal [GE] junction adenocarcinoma, and gastric. For the most part in Western countries, in my clinic, two-thirds to 70% of the patients are GE junction adenocarcinomas. As we mentioned, we’re not screening routinely for these patients, so they’re for the most part presenting locally advanced or overt metastatic disease by the time they present.
Increasing awareness in terms of the symptoms that we’re talking about, chronic reflux, and symptoms from a Western diet, Caucasian, diabetes, chronic reflux, and obesity, are types of associated factors. Primary care physicians know how to act on these things earlier rather than waiting for several months to years before it’s too late.
The only other comment I’d make is that the different studies that we’re going to be talking about, they really have heterogeneity in terms of the eligibility for accrual to the study. Some of them overlap in squam and adeno, some of them overlap in GE junction and gastric. We know from the previous studies that they have different sensitivities to immunotherapy, so we need to look at their contributions and the evidence.
Johanna Bendell, MD: Very good. We know that in the west, most patients are diagnosed with advanced metastatic disease. Yelena, what is the general approach when we see a patient here in the United States in the west? How are we going to look at that patient who presents with advanced or metastatic disease and treatment options in the course?
Yelena Janjigian, MD: In the United States, and the west in general, the biggest differences in approach to our Japanese, North Korean, and colleagues is the use of perioperative versus adjuvant therapy in localized and resectable disease in the United States because the tumors are more proximal, gastroesophageal junction adenocarcinoma tumors, they’re more aggressive in nature, and if surgery is possible, they often require total gastrectomy. It is a greater challenge to administer adjuvant therapy.
Therefore, because the patients are more nutritionally compromised, they often take a month or 2 months to recover fully after the operation, and at that point they lost 10% to 15% of their total body weight. It’s a big challenge to administer the adjuvant therapy in that setting. Therefore, unlike our east and Asian colleagues, we tend to administer more therapy in the neoadjuvant or preoperative setting. It gives an advantage of understanding tumor biology, whether or not the therapy is effective in vivo assessment with imaging and so on.
Also, this precludes patients from having unnecessary surgery. If the disease is still aggressive, then within a few cycles of therapy occult metastatic disease is detected, often that was subacute before. Again, you’re not wasting opportunity to cure your patient, you’re preventing them from having an unnecessary surgery.
The second point is, and increasingly you see, looking at first-line studies conducted in stage IV disease in Asia versus the west and the rest of the world, is the use of second- and third-line therapy.
In the world, outside of Japan and Korea, probably 30% to 40% of patients receive second- and third-line therapy. In fact, if you were watching European Society for Medical Oncology yesterday, it kept coming up. How is that possible? Is that really a real-world data, and are these studies somehow confounded? The truth is that it is the real-world data. Unfortunately, there are various factors that we’re going to discuss later in terms of disease burden and patient’s functional status but also somewhat in an annalistic approach. Prevalent among oncologists and patients, outside of Japan and Korea, the majority of patients do not receive second-line therapy and third-line therapy, and that’s really an important pivotal point that we need to change as we understand more about this disease.
Johanna Bendell, MD: When we think about what we’re going to use in the first line, I know we’re going to get very much into the discussion a little bit later, but in general, what are general principles for treatment? I mean we know in colon cancer we would give chemotherapy. Then we’d go to maintenance. How do you approach that patient with metastatic disease in the first line in terms of how you’re going to set the stage for treatment down the line?
Yelena Janjigian, MD: Functional status is number 1. The earlier you test for biomarkers the better; and I always tell my patients, “Know your mutation status; ask your oncologist.” Knowing the silver lining of this whole global pandemic is that telehealth and telemedicine has really taken off in oncology in particular. I often see patients from all over the world virtually or from over the United States. Biomarker analysis, and also knowing the disease biology, is critical. Obviously 1 drug is better than no therapy. Baseline 5-FU–based therapy is the cornerstone of all gastrointestinal tumors, gastric cancer, and esophagus cancer.
Two drugs are better than 1 drug. Additionally, a third-drug therapy, although there’s still some data to support it, increasingly now the emerging data suggests that immune checkpoint inhibitors and other targeted therapies should be used in first-line setting. It’s becoming a challenge to build on third-drug baseline chemotherapies.
The majority of our patients, and, again, even though younger and younger patients are presenting to us, as specialists, most of our patients are still in their 60s or 70s. They can be frail with multiple comorbidities. Two-drug combination with FOLFOX [folinic acid, fluorouracil, oxaliplatin] or 5-FU [5-fluorouracil], oxaliplatin; or occasionally, like you said, to be oxaliplatin, is what most patients get.
So, Ken, how do you treat patients? How’s your treatment approach in Japan different from what we do here?
Ken Kato, MD, PhD: As they are in remission, so we use a drug combination with fluoropyrimidine plus an agent for the first-line treatment for the gastric cancer as well. The patients who have gastric cancer have a comorbidity such as a disorder for eating and appetite loss. So, in Japan, so they have a tendency to move to the oxaliplatin from the cisplatin.
The oxaliplatin had the adverse event of the peripheral neuropathy. We frequently use the secondary chemotherapy. In Japan, 80% of the patients receive the secondary chemotherapy with paclitaxel.
We should use the oxaliplatin carefully. Usually we use the 2-drug combination with platin. And you know the S-1 is mostly used for the gastric cancer patient and the fluoropyrimidine agent in Japan.
Transcript Edited for Clarity