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Pivotal Trials Lead to Significant Implications in Gastric/GEJ Cancer

Brandon Scalea
Published: Wednesday, Mar 06, 2019

Timothy L. Cannon, MD

Timothy L. Cannon, MD

Several pivotal studies have recently read out in the gastric/ gastroesophageal junction (GEJ) cancers space—all of them bearing clinical implications for oncologists, said Timothy L. Cannon, MD, and future research will likely focus on bringing novel combinations forward in the paradigm.

In February 2019, the FDA approved TAS-102 (trifluridine/tipiracil; Lonsurf) for the treatment of adult patients with metastatic gastric or GEJ adenocarcinoma who were treated with ≥2 prior lines of chemotherapy. The approval was based on positive data from the phase III TAGS trial, results of which demonstrated a median overall survival (OS) of 5.7 months for patients treated with TAS-102 versus 3.6 months for those who were given placebo.1 Further, the 1-year OS rate with TAS-102 was 21% versus 13% with placebo. The 6-month progression-free survival rates were 15% and 6%, respectively.

However, there has been recent interest in investigating the potential of pembrolizumab (Keytruda) in this setting, as the agent has shown antitumor activity in patients with pretreated gastric/GEJ cancer. As such, in the KEYNOTE-061 trial, patients were randomized to receive either pembrolizumab monotherapy or paclitaxel.

Although the median OS was 9.1 months versus 8.3 months in favor of the checkpoint inhibitor, this difference was not determined to be statistically significant.2 However, for patients with good performance status and whose tumors have high PD-L1 expression, it may be reasonable to administer this agent prior to chemotherapy, according to Cannon.

Meanwhile, the antiangiogenic agent ramucirumab (Cyramza) has maintained its role in the second-line setting. However, in the frontline setting, results from the phase III RAINFALL study, did not demonstrate any benefit to adding ramucirumab to standard frontline chemotherapy in patients with gastric cancer. In the intent-to-treat population, median PFS was 5.85 months in the ramucirumab arm compared with 5.55 months in the control arm. Although the addition of ramucirumab resulted in a 25% reduction in the risk of disease progression or death, it did not result in improved OS.3

In an interview during the 2019 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, Cannon, a medical oncologist at Inova Medical Group, discussed how these pivotal clinical trials have impacted the gastric cancer treatment landscape.

OncLive®: What are some recent clinical trials in this space worth highlighting?

Cannon: I focused on a few larger trials that I thought had the most significant clinical implications for oncologists in 2019. The first one is the TAGS trial, which is a phase III study comparing the use of TAS-102 with placebo in the third-line treatment of [patients with] gastric cancer. That trial showed an OS benefit of approximately 2 months. The therapy was generally well tolerated other than some bone marrow suppression. As such, [TAS-102] may be a reasonable treatment option in the third-line setting for these patients.

The second study I spoke about was KEYNOTE-061, a comparison of second-line pembrolizumab versus second-line paclitaxel in gastric or GEJ adenocarcinoma. In that study, pembrolizumab did not show a survival benefit compared with chemotherapy, although it was a little bit better tolerated. The OS was 9.1 months in the pembrolizumab arm and 8.3 months in the paclitaxel arm. Therefore, what I have concluded from that is, while pembrolizumab is a reasonable second-line option, so is chemotherapy. Of course, the trial failed to show a superiority for immunotherapy in that setting. That trial, by the way, only included patients who expressed PD-L1 in their tumors.


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TitleExpiration DateCME Credits
Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
Community Practice Connections™: Navigating New Sequencing Challenges for the Treatment of Hepatocellular CarcinomaAug 30, 20191.5
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