FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer.

On January 19, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. The primary endpoint was overall response rate (ORR) by RECIST 1.

FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement.

On April 17, 2020, the FDA granted accelerated approval to pemigatinib (PEMAZYRE, Incyte Corporation) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. Approval was based on FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial. Efficacy was based on 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy and had an FGFR2 gene fusion or rearrangement.

FDA Approval Summary: Nivolumab for the Adjuvant Treatment of Adults with Completely Resected Esophageal/Gastroesophageal Junction Cancer and Residual Pathologic Disease.

The FDA approved nivolumab on May 20, 2021, for the adjuvant treatment of completely resected (negative margins) esophageal or gastroesophageal junction cancer (EC/GEJC) in patients who had residual pathologic disease following chemoradiotherapy. The approval was based on data from the double-blind CheckMate 577 trial, which randomly allocated patients to receive nivolumab or placebo. Disease-free survival (DFS) was the primary endpoint.

Effect of the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation Therapy for Patients With Esophageal Cancer: The NRG Oncology RTOG 0436 Phase 3 Randomized Clinical Trial.

Importance: The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain.

Objective: To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma.

Design, Setting, And Participants: A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus.

A final report of a phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis with a dose escalation in ovarian and fallopian tube cancers.

Background: The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV).

Methods: Patients were treated with veliparib, 40-400mg orally BID on days 1-21 of 3 28-day cycles on 6 dose levels.

Primary Gross Tumor Volume is an Important Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Trimodality Therapy.

Purpose: This study investigated the relationship between tumor volume and outcomes in patients receiving trimodality therapy for locally advanced esophageal cancer.

Methods: Between 2001 and 2012, 67 patients treated for esophageal cancer with chemoradiotherapy followed by esophagectomy who had available gross tumor volume (GTV) information were analyzed (35 node-negative, 32 node-positive patients with primary and nodal GTV contoured as separate regions of interest). All gross tumor volumes (GTVs) were contoured at the time of radiotherapy treatment planning.

A Phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis.

Purpose: The combination of low-dose radiotherapy with PARP inhibition has been shown to enhance antitumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), a small-molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies.

Experimental Design: Patients were treated with veliparib (80-320 mg daily) for a total of 3 cycles.

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

Introduction: The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery.

Materials And Methods: At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.

Neoadjuvant paclitaxel poliglumex, cisplatin, and radiation for esophageal cancer: a phase 2 trial.

Purpose: To evaluate the pathologic complete response (CR) rate and safety of paclitaxel poliglumex (PPX), cisplatin, and concurrent radiation for patients with esophageal cancer.

Patients And Methods: Patients with adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction with no evidence of distant metastasis received PPX (50 mg/m(2)/wk) and cisplatin (25 mg/m(2)/wk) for 6 weeks with 50.4 Gy concurrent radiation.

Outcomes after trimodality therapy for esophageal cancer: the impact of histology on failure patterns.

Objectives: This retrospective analysis of patients undergoing neoadjuvant chemoradiation followed by surgical resection was performed to determine if histology or pathologic response affected local-regional control (LRC), survival outcomes or patterns of failure.

Methods: We performed a review of 164 patients who underwent neoadjuvant chemoradiation followed by surgical resection from 1992 to 2006 for esophageal cancer. Information on patient characteristics, pathologic response, failure patterns, and survival was collected.

Safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of sorafenib and tanespimycin.

Purpose: Heat shock protein (Hsp) 90 inhibition affects the Raf kinase signaling pathway and could enhance antitumor effects of sorafenib, a Raf kinase inhibitor. The combination of sorafenib and tanespimycin [17-allyl-amino-geldanamycin (17-AAG); NSC 330507/KOS-953] was evaluated in a phase I trial with the primary objective of defining a phase II dose.

Patients And Methods: The dose cohorts consisted of fixed continuous oral dosing of 400 mg sorafenib twice daily, starting at 14 days before tanespimycin, which was administered intravenously at escalating doses (starting at 300 mg/m,(2) with 50 mg/m(2) increments), on days 1, 8, and 15 in a 28-day cycle.