GIST

Here's a look back on the FDA happenings for the month of August 2019, including FDA approvals, priority reviews, and breakthrough designations.

John L. Marshall, MD, spoke with a group of physicians during a Targeted Oncology live case-based peer perspectives discussion on the different classes of agents available to treat patients with gastrointestinal cancers.

Management of neuroendocrine liver metastases relies on many treatment modalities, ranging from surgery to ablation. Clinicians have in their armamentarium interventional radiology techniques that use regional and systemic treatments spanning a diverse group of biologic, cytotoxic, and targeted agents.

Howard S. Hochster, MD, discusses the role of TAS-102 in patients with gastric/gastroesophageal junction or colorectal cancer in comparison to fluorouracil.

Ripretinib demonstrated a significantly improved progression-free survival compared with placebo in patients with gastrointestinal stromal tumors being treated in the fourth-line setting or beyond, according to topline results from the phase III INVICTUS trial. An NDA for ripretinib is planned for the first quarter of 2020. 

The FDA has granted a priority review to a New Drug Application for avapritinib as a treatment for adult patients with <em>PDGFRA</em> exon 18&ndash;mutant gastrointestinal stromal tumors, regardless of prior therapy, and in the fourth-line setting for GIST.

Laura Dawson, MD, FRCPC, FASTRO, has been selected as the president-elect of the American Society for Radiation Oncology and will begin her term at the society&rsquo;s 61st Annual Meeting, which is being held in Chicago, Illinois on September 15-18.

The investigational agent SM-88 demonstrated promising survival in the phase II TYME-88-Panc study in patients with advanced pancreatic cancer.^1,2&nbsp;The&nbsp;oral modified dysfunctional tyrosine induced a median overall survival of 6.4 months in patients.<br /> &nbsp;

Based on the ongoing and positive data observed with VEGFR targeted therapies, novel tyrosine kinase inhibitors and those already approved for other disease indications may become available to patients with bone and soft tissue sarcomas.

A prefilled syringe of&nbsp;lanreotide has been approved by the FDA to&nbsp;enable healthcare providers to administer the injection easier to adults with unresectable, well or moderately differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors.

ABP 980, a trastuzumab biosimilar, has been approved by the FDA&nbsp; for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, marking the fifth approval by the agency for a trastuzumab biosimilar.

During a recent&nbsp;<em>Targeted Oncology&nbsp;</em>live case-based peer perspectives presentation, Tanios Bekaii-Saab, MD, discussed with a group of physicians the treatment options for patients with gastrointestinal cancers and the characteristics that influence his decision making. Bekaii-Saab explained his clinical decisions based on the case scenario of one patient with colorectal cancer and one with hepatocellular carcinoma.

The novel bispecific antibody ZW25 has been granted a fast track designation by the FDA for the treatment of patients with HER2-overexpressing gastroesophageal adenocarcinoma to be used in combination with standard-of-care chemotherapy.

Comparable efficacy and minimized adverse events were seen with a lower dose of&nbsp;oxaliplatin (Eloxatin) and capecitabine (Xeloda)&nbsp;in elderly and frail patients with advanced gastroesophageal cancer, according to findings to be presented during&nbsp;the 2019 American Society of Clinical Oncology Annual Meeting.

Findings from a study of tumor samples collected from patients with pancreatic ductal adenocarcinoma revealed that 17% of tumors harbored a known genomic alteration for which targeted therapies have already been developed, conferring feasibility to implementing precision medicine in a disease that has seen little progress in the development of effective therapeutic agents.

The success of chimeric antigen receptor T-cell therapy observed in hematologic malignancies has not yet translated into the solid tumor setting; however, efforts continue to try to bring this new modality into the treatment paradigm for solid tumors, including pancreatic cancer.&nbsp;

A fourth trastuzumab biosimilar has been granted approval by the FDA. The approval was for PF-05280014 for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

Based on data from the phase III TAGS trial, TAS-102 has been approved by the FDA as a treatment for&nbsp;adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Merck,&nbsp;the developer of pembrolizumab, has announced that the coprimary endpoints of the&nbsp;KEYNOTE-240 trial were not met, as adding the agent&nbsp;to best supportive care failed&nbsp;to improve&nbsp;progression-free or overall survival in patients with advanced hepatocellular carcinoma who were previously treated with systemic therapy.

Achieving an objective response to TKI therapy was associated with longer overall survival in patients with&nbsp;previously untreated hepatocellular carcinoma, according to findings of a retrospective analysis presented during the 2019 Gastrointestinal Cancers Symposium.

Combined BRAF and MEK inhibition induced a promising response rate and survival rates among patients with&nbsp;<em>BRAF&nbsp;</em>V600E&ndash;mutated biliary tract cancer (BTC), according to the results of the ROAR trial that were presented&nbsp;during the 2019 Gastrointestinal Cancers Symposium.

SB3, a trastuzumab biosimilar, has been granted FDA approval&nbsp;for the treatment of patients with HER2-overexpressing breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma.

Based on findings from the phase I/II NivoRam study, investigators at the 2019 Gastrointestinal Cancers Symposium reported that the combination of&nbsp;nivolumab and ramucirumab is active in patients with&nbsp;previously treated advanced gastric adenocarcinoma.

In findings reported at the&nbsp;2019 Gastrointestinal Cancers Symposium, 67% of patients with untreated metastatic HER2-positive esophagogastric adenocarcinoma treated with&nbsp;the combination of pembrolizumab, trastuzumab, and chemotherapy&nbsp;remained progression-free at 6 months.

According to findings from the&nbsp;KEYNOTE-181 trial, pembrolizumab demonstrated a significant improvement in overall survival in patients with PD-L1&ndash;positive advanced or metastatic esophageal or esophageal junction carcinoma who progressed on standard therapy, marking the first time a PD-1 inhibitor has demonstrated a survival improvement in this patient population.