ESMO 2019: Dr. Bekaii-Saab Highlights Important Trials in GI Malignancies

Tanios S. Bekaii-Saab, MD, FACP, medical oncologist, medical director, Cancer Clinical Research Office, vice chair and section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses data presented at the 2019 ESMO Congress in gastrointestinal (GI) malignancies.

In hepatocellular carcinoma (HCC), the combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) showed an improvement in progression-free survival (PFS) in patients with unresectable disease, according to data from two small clinical trials. In the randomized part of trial, patients who received the combination experienced a 45% reduction in the risk of disease progression or death compared with atezolizumab monotherapy. Notably, the combination is being compared with sorafenib (Nexavar) in the frontline setting in the phase III IMbrave150 study.

Data from the IMbrave150 study are eagerly anticipated, despite data from the phase III CheckMate-459 trial which indicated that frontline nivolumab (Opdivo) did not lead to a statistically significant improvement in overall survival (OS) compared with sorafenib in patients with unresectable HCC.

In the phase III ClarIDHy trial, investigators evaluated ivosidenib (Tibsovo) versus placebo in patients with advanced cholangiocarcinoma harboring an IDH1 mutation. Approximately 15% to 20% of patients will harbor a mutation in IDH1, notes Bekaii-Saab. Ivosidenib led to a median PFS of 2.7 months versus 1.4 months with placebo (HR, 0.37; 95% CI, 0.25-0.54; P <.001).

Additionally, data from the phase II FIGHT-202 trial showed that pemigatinib led to a 35.5% objective response rate in patients with previously treated locally advanced or metastatic cholangiocarcinoma with an FGFR2 rearrangement or fusion (cohort A). Median PFS was 6.8 months in cohort A compared with 2.1 months and 1.7 months in patients with other FGF/FGFR alterations (cohort B) and no FGF/FGFR alterations (cohort C), respectively.

Going forward, HER2 and BRAF could become additional targets in cholangiocarcinoma, says Bekaii-Saab.

Moreover, the final analysis of the phase III ATTRACTION-3 study demonstrated superior overall survival (OS) with nivolumab versus standard chemotherapy in patients with previously treated advanced esophageal cancer. Median OS was 10.9 months versus 8.4 months in the nivolumab and chemotherapy arms, respectively (HR, 0.77; 95% CI, 0.62-0.96; P =.019). Although these data are encouraging, Bekaii-Saab states that the majority of patients were primarily of Asian descent.

The optimal sequencing of immune checkpoint inhibitors is still under investigation, says Bekaii-Saab—–adding that data from the phase III ATTRACTION-3 trial could shed light on the optimal use of these agents in esophageal cancer.

Finally, data from the phase III BEACON CRC trial, the phase II MOUNTAINEER trial, and the phase II BACCI trial are enhancing the use of precision medicine in metastatic colorectal cancer (mCRC), says Bekaii-Saab.

In the BEACON trial, investigators reported an OS of 9.0 months with the triplet of encorafenib (Braftovi), binimetinib (Mektovi), and cetuximab (Erbitux) compared with 5.4 months with cetuximab/irinotecan-containing treatment in patients with BRAF V600E-mutated mCRC (HR, 0.52; 95% CI, 0.39—0.70; P < .0001).

In the MOUNTAINEER trial, investigators evaluated tucatinib plus trastuzumab (Herceptin) in patients with HER2-amplified mCRC. Initial data showed a 52.2% response rate, median OS of 18.7 months, and PFS of 8.1 months with the combination.

In the BACCI trial, patients with microsatellite stable disease were randomized 2:1 to receive capecitabine, bevacizumab, and atezolizumab, or capecitabine, bevacizumab, and placebo. According to Bekaii-Saab, the addition of atezolizumab to capecitabine/bevacizumab led to a significantly longer PFS versus placebo plus capecitabine/bevacizumab.

PD-1 vaccines are also under development, explains Bekaii-Saab, and early data suggest they will be at least as effective as immune checkpoint inhibitors.

Going forward, Bekaii-Saab is hopeful to see continued growth in this field with precision medicine.