Brandon Smaglo, MD, FACP
With a new FDA approval in the third-line setting for patients with gastric cancer and research hinting at the opportunity for a personalized medicine approach, the space is bursting with new data to consider.
Regarding the advanced setting, results from the phase III TAGS trial, in which investigators evaluated trifluridine/tipiracil (TAS-102; Lonsurf) in heavily pretreated patients with metastatic gastric cancer, showed that the oral therapy is effective and has a manageable safety profile regardless of prior gastrectomy.
Median overall survival (OS), which was the primary endpoint, was 5.7 months for those who received TAS-102 compared with 3.6 months in those who were given placebo (HR, 0.69; P
The 1-year OS rate for those in the TAS-102 arm was 21% compared with 13% for those in the placebo arm.
“While the survival advantage was real, it was also pretty slight,” said Brandon Smaglo, MD, FACP, an assistant professor and medical director of Hematology/Oncology at the Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine. “But the fact that it was so well tolerated makes it very attractive.”
These findings led to the February 2019 FDA approval of TAS-102 for adult patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who were previously treated with ≥2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, and HER2/neu-targeted therapy, if appropriate.2
Findings from the phase III KEYNOTE-061 trial, which compared pembrolizumab (Keytruda) with paclitaxel in patients with advanced gastric/GEJ cancer who progressed on first-line chemotherapy with a platinum and fluoropyrimidine, did not show a significant survival benefit with the PD-1 inhibitor.3
However, data did suggest that there may be gradations of PD-L1 positivity allowing for the selection of patients who could potentially benefit from pembrolizumab, said Smaglo.
“To be able to make treatment decisions based upon that is really revolutionary, we'll see a lot more information from that study or from that approach in the near future,” he added.
However, more work is needed in the adjuvant space, where investigators have not moved the bar for over a decade.
“Our standard of care for the management of adjuvant treatment in gastric cancer goes back to 2 studies—one from 2001, one from 2006,” said Smaglo. “That we haven't moved the bar since then is disappointing, but I'm hopeful that a lot of what we're seeing in the advanced space will also move into the adjuvant space so that we can finally achieve better outcomes in a more consistent manner for those patients as well.”
In an interview during the 2019 OncLive®
State of the Science Summit™ on Gastrointestinal Cancers, which took place just prior to the recent TAS-102 approval, Smaglo highlighted investigational treatment approaches for patients with gastric cancer and called for further research in the adjuvant setting to move the needle forward.
OncLive: Could you discuss the TAGS trial and the key findings?
: TAGS was an interesting trial, largely because it was a study in the very late-line treatment of [patients with] gastric cancer—a third-line of treatment or higher. In many cancers, we do have multiple lines of therapy, but in gastric cancer, we've really been focused a lot on first-line therapy, with only a little bit [of a focus] on second-line treatment. So, to have a study that was focused on that late-line [of therapy] was very unique and it turned out to be very important for the management of our patients.
There are a couple of things that I take away from that study. Number one, the therapy that is used is a very easy therapy for many patients to tolerate, particularly compared with doublet or triplet combinations of chemotherapy drugs. [Second], it's a therapy that patients take as a pill.
For [a patient] who may have been on therapy for 1 year or more—[who had] to constantly come in for infusions and deal with the dregs of that back-and-forth [travel]—to be able to take a medicine at home and still get good oncologic care is really impressive. Also, for [a patient] to have perhaps a few months of a survival advantage with a therapy is oftentimes questionable, but to get that advantage and still have a very good quality of life and [be able to maintain that] good quality of life is very important, and that seemed to be demonstrated by the TAGS study.