GIST

In January 2020, the FDA approved new treatment options in gastrointestinal stromal tumors, bladder cancer, and epithelioid sarcoma. The FDA also granted several Priority Review Designations, orphan drug designations, and a Fast Track designation, as well as a Breakthrough Therapy designation.

The FDA has extended the Prescription Drug User Fee Act date by 3 months for the new drug application of avapritinib from February 14, 2020, to May 14, 2020, the manufacturer, Blueprint Medicines Corporation, announced in a news release. The NDA was seeking accelerated approval for the kinase inhibitor for the treatment of adults with fourth-line gastrointestinal stromal tumors.

In an interview with Targeted Oncology, Vincent Chung, MD, discussed the findings from the pilot trial evaluating the addition of dietary supplements to combination chemotherapy in patients with unresectable pancreatic cancer. He also highlighted the importance of these findings and the next steps necessary to evaluate the role of supplements in pancreatic cancer further.

Promising antitumor activity with durable responses were demonstrated with the combination of nivolumab and ramucirumab plus paclitaxel in a phase II study of patients with advanced gastric cancer, which wsa presented at the 2020 Gastrointestinal Cancers Symposium. Among patients treated with the combination, the objective response rate was 37.2%, and all responders had a partial response.

Overall survival was meaningfully improved with treatment of pembrolizumab in first and later lines for patients with advanced gastric/gastroesophageal junction cancer with a high number of PD-L1–expressing cells in the tumor, lymphocytes, and macrophages compared with chemotherapy.

A subset of patients with GI cancers harboring&nbsp;<em>NTRK</em>&nbsp;gene fusions had positive responses to selective TRK inhibition with larotrectinib, confirming efficacy of the agent in this group. The results of the confirmatory trial were recently reported the 2020 Gastrointestinal Cancers Symposium.

A phase Ib/II clinical trial of the experimental anti-mitochondrial drug devimistat in combination with cisplatin and gemcitabine has been initiated in patients with biliary tract cancer, according to a press release from Rafael Pharmaceuticals, Inc. The company will collaborate with Michigan Medicine to proceed with the randomized multicenter clinical trial.

The FDA has approved avapritinib for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor who harbor platelet-derived growth factor receptor alpha exon 18 mutation, including PDGFRA D842V mutations. This approval makes avapritinib the first precision medicine therapy for a genomically defined population of patients with GIST, according to a press release from the Blueprint Medicines Corporation.

Aiwu Ruth He, MD, discusses the current role of immune checkpoint inhibitors in upper gastrointestinal and gastric cancers and which patients are most likely to benefit from the anti&ndash;PD-1 agents.

In December 2019, the FDA approved a number of new treatments in lung cancer, pancreatic cancer, urothelial carcinoma, breast cancer, and prostate cancer. A&nbsp;tissue complete assay was also approved by the FDA for use in a clinical trial evaluating pembrolizumab.

Margaret von Mehren, MD, discusses the rationale for evaluating ripretinib in patients with heavily pretreated advanced GIST in&nbsp;the phase III INVICTUS trial, which was presented at the ESMO Congress 2019.

The first half-yearly follow-up&nbsp;results from a phase I study of ilixadencel monotherapy in patients with advanced gastrointestinal stromal tumors will be presented by Alex Karlsson-Parra, MD, PhD on February 6, 2020, during poster session A, at the Clinical Immuno-Oncology Symposium, according to a press release from Immunicum AB, where Karlsson-Parra serves as the chief executive officer.<br /> &nbsp;

The target number of patients with advanced gastrointestinal stromal tumors have been enrolled in the phase III VOYAGER study in China, which is evaluating the safety and efficacy investigational drug avapritinib in the third- or fourth-line settings, according to a press release from CStone Pharmaceuticals.<br /> &nbsp;

A New Drug Application for ripretinib was submitted to the FDA for the treatment of patients with advanced gastrointestinal stromal tumor who have received a prior treatment of imatinib, sunitinib, and regorafenib, according to a press release from Deciphera Pharmaceuticals, Inc.

Benjamin Weinberg, MD, assistant professor of medicine, and attending physician, Georgetown University Hospital, Medstar Health, discusses the overall prognosis of patients with gastrointestinal stromal tumors.

Timil Patel, MD, discusses how to sequence therapies in a patient with rectal cancer with a single lung nodule.

Given the frequency of <em>FGFR2</em>&nbsp;alterations in intrahepatic cholangiocarcinoma, investigators have identified it as a potential prognostic indicator of survival and a rational target of systemic cancer therapies.

Winston Tan, MD, discusses the emergence of novel agents for the treatment of patients with gastrointestinal stromal tumors, namely agents like avapritinib and ripretinib, which have shown promise in ongoing clinical trials.<br /> &nbsp;

TT-00420, an investigational spectrum-selective multiple kinase inhibitor received an orphan drug designation from the FDA for the treatment of cholangiocarcinoma, TransThera Biosciences Co. Ltd announced in a press release.

Daniel Catenacci, MD, discusses how he makes decisions with immunotherapeutic agents for the treatment of patients with gastroesophageal junction cancer. He says he bases his sequencing decisions on a number of factors.

The phase III VOYAGER study may soon introduce a new treatment option for patients with locally advanced metastatic or unresectable gastrointestinal stromal tumors, a patient population with an unmet need for novel agents that are durable and can target specific drivers. The trial is looking at the efficacy of novel drug avapritinib versus standard-of-care regorafenib.<br /> &nbsp;

The FDA plans to split up the submitted New Drug Application for avapritinib into 2 separate NDAs in the treatment of 2 different populations of patients with gastrointestinal stromal tumors, according to a press release from Blueprint Medicines.

Pamela L. Kunz, MD, discusses the most recent FDA approval of Lutathera (lutetium [Lu 177] dotatate) for the treatment of patients with gastroenteropancreatic NETs (GEP-NETs), including foregut, midgut, and hindgut tumors.

Following the 2019 ESMO Congress, experts across various fields highlighted some next steps and how these treatment options will improve the treatment landscape for patients with ovarian, lung, breast, GI, or GU cancers. Overall, the abstracts presented at this year&rsquo;s meeting will change the treatment paradigm in a number of patient populations.

In the phase III INVICTUS trial, ripretinib, a novel KIT and PDGFRA inhibitor, demonstrated a dramatic improvement in progression-free survival compared with placebo in heavily pretreated patients with heavily advanced gastrointestinal stromal tumors, according to data presented at the 2019 ESMO Congress.