Gastric Cancer: Global Perspectives on Maintenance Therapy

Kei Muro, MD: In gastric cancer, I do not think the concept of maintenance therapy has been accepted yet, unlike in colon and lung cancer. However, due to the toxicity of platinum agents such as cisplatin and oxaliplatin, it cannot be used for long periods. Fluoropyrimidine monotherapy is often used as a single agent during the first-line treatment. This will result in performing maintenance therapy. This is continuation maintenance therapy, so to speak.

In terms of switch maintenance therapy, there have been trials with IO [immunotherapy]. Both ipilimumab as a CTLA-4 [cytotoxic T-lymphocyte–associated protein 4] antibody and avelumab as a PD-L1 [programmed death-ligand 1] antibody, tested in JAVELIN Gastric 100, have had negative results in overall survival. Maintenance strategy for advanced gastric cancer has not been established at this moment. However, theoretically, and considering the mechanism of action of IO, a maintenance strategy with IO treatment is not a wrong direction to go.

Salah-Eddin Al-Batran, MD: Maintenance therapy in gastric cancer is not a standard of care yet. Despite this, many experts and oncologists use a type of maintenance therapy. The decision to go for maintenance therapy is based on the individual characteristics of the patient, like a patient’s perspectives and response, etc. Many oncologists de-escalate the chemotherapy regimen from a triplet to a doublet, or from a doublet to a monotherapy, after 4, 6, or 8 cycles of treatment to reduce toxicity. However, there are no studies to show that maintenance therapy is more active than no maintenance therapy. Personally, in patients who are HER2 [human epidermal growth factor receptor 2]-positive, I like to eliminate the platinum and continue treatment with a HER2 antibody plus fluoropyrimidine after approximately 8 cycles of treatment. But there is no clear standard of care in terms of a maintenance treatment.

Daniel V. Catenacci, MD: With respect to the issue of maintenance therapy for gastroesophageal cancer, we don’t have a lot of evidence to support this. That said, we do extrapolate from other tumor types, such as colorectal cancer, where we have the OPTIMOX studies. OPTIMOX-1 dropped oxaliplatin and continued fluoropyrimidine, intermittently adding oxaliplatin back in. The OPTIMOX-2 study initiated a complete chemotherapy holiday and then intermittently added chemotherapy back on.

We have data to show, especially in OPTIMOX-1, that by dropping oxaliplatin we can limit the buildup of cumulative neurotoxicity, which is one of the main issues, and therefore increase the longevity of using oxaliplatin over time by intermittently adding it back in. In those studies, it was added routinely in a regimented manner: 2 months on, 2 months off. In our practice, both in colorectal cancer and in gastroesophageal cancer, I stop oxaliplatin after 4 months, which is usually the time at which neuropathy is really starting to creep in. Patients then go on a fluoropyrimidine monotherapy, whether it’s IV [intravenous] or oral. I reserve the reintroduction of oxaliplatin for when there is actual RECIST [Response Evaluation Criteria in Solid Tumors] progression, tumor markers start to increase, symptoms increase, or there is a combination thereof.

I tell my patients that it can be years before we have to reintroduce oxaliplatin. On the other hand, it could be after just 2 months of being off oxaliplatin that you start to see signs that you need to start thinking about reintroducing it. The only other thing to say is that in the HER2-positive tumor type, which is about 15% of our patients with gastroesophageal adenocarcinoma, we would include trastuzumab therapy along with fluoropyrimidine as maintenance and then intermittently add the platinum agent back in.

I will say that about 50% of patients are still not able to experience reintroduction of the platinum agent in my practice, and that’s because they still have residual neuropathy that we don’t want to push. At that point, we would switch to second-line therapy, but there are a number of patients who you can reintroduce oxaliplatin in and regain control for a period and not use up later lines of therapy.

Transcript edited for clarity.