Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results.

Cellular immunity, mediated by tumor antigen-specific CD4 and CD8 T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (n = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.

Real-World Analysis of Irinotecan With or Without Fluorouracil in the Second-Line Treatment of Metastatic Colorectal Cancer.

Background: The most used first-line chemotherapy backbone for metastatic colorectal cancer (mCRC) is fluoropyrimidine and oxaliplatin. Despite limited data supporting the superiority of second-line FOLFIRI over irinotecan, guidelines continue to endorse both options, and FOLFIRI remains more commonly used.

Patients And Methods: This study used a nationwide electronic health record-derived deidentified database to select patients with mCRC who received first-line treatment with fluoropyrimidine and oxaliplatin with or without a biologic agent, and second-line treatment with irinotecan ± fluorouracil with or without a biologic agent.

Pathological Features Associated with Lymph Node Disease in Patients with Appendiceal Neuroendocrine Tumors.

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis.

Relacorilant plus nab-paclitaxel for the treatment of metastatic pancreatic ductal adenocarcinoma: results from the open-label RELIANT study.

Background: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines.

Patients And Methods: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles.

Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial.

Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing.

Phase 1 study to determine the safety and dosing of autologous PBMCs modified to present HPV16 antigens (SQZ-PBMC-HPV) in HLA-A*02+ patients with HPV16+ solid tumors.

We conducted a dose escalation Phase 1 study of autologous PBMCs loaded by microfluidic squeezing (Cell Squeeze technology) with HPV16 E6 and E7 antigens (SQZ-PBMC-HPV), in HLA-A*02+ patients with advanced/metastatic HPV16+ cancers. Preclinical studies in murine models had shown such cells resulted in stimulation and proliferation of antigen specific CD8+ cells, and demonstrated antitumor activity. Administration of SQZ-PBMC-HPV was every 3 weeks.

A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.

Purpose: Guanylyl cyclase C (GCC) is highly expressed in several gastrointestinal malignancies and preclinical studies suggest that it is a promising target for antibody-based therapeutics. This phase I trial assessed the safety and tolerability of TAK-164, an investigational, anti-GCC antibody-drug conjugate (NCT03449030).

Methods: Thirty-one patients with GCC-positive, advanced gastrointestinal cancers received intravenous TAK-164 on day 1 of 21-day cycles.

Neoadjuvant treatment of localized pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the deadliest malignancies worldwide and its incidence is rising in the United States. The only potential curative treatment for this disease is surgical resection, however, due to the lack of an effective screening strategy, the majority of patients present with advanced or metastatic disease which preclude resectability. Further, the best clinical outcomes occur in those patients that receive multimodality treatment with surgical resection combined with chemotherapy with or without the addition of radiation therapy.

WEE1 Inhibition in Combination With Targeted Agents and Standard Chemotherapy in Preclinical Models of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with high incidences of p53 mutations. AZD1775 (adavosertib, previously MK-1775) is a small molecule WEE1 inhibitor that abrogates the G2M checkpoint and can potentially synergize with DNA damaging therapies commonly used in PDAC treatment. The purpose of this study was to identify combination partners for AZD1775, including standard chemotherapy or targeted agents, in PDAC preclinical models.

Impact of Radiation Dose on Postoperative Complications in Esophageal and Gastroesophageal Junction Cancers.

The impact of radiation prescription dose on postoperative complications during standard of care trimodality therapy for operable stage II-III esophageal and gastroesophageal junction cancers has not been established. We retrospectively reviewed 82 patients with esophageal or gastroesophageal junction cancers treated between 2004 and 2016 with neoadjuvant chemoradiation followed by resection at a single institution. Post-operative complications within 30 days were reviewed and scored using the Comprehensive Complication Index (CCI).

Antibody drug conjugates under investigation in phase I and phase II clinical trials for gastrointestinal cancer.

Introduction: Antibody drug conjugates (ADCs) represent a developing class of anticancer therapeutics which are designed to selectively deliver a cytotoxic payload to tumors, while limiting systemic toxicity to healthy tissues. There are several ADCs which are currently in various stages of clinical development for the treatment of gastrointestinal malignancies.

Areas Covered: We discuss the biologic rationale and review the clinical experience with ADCs in the treatment of gastrointestinal malignancies, summarizing the pre-clinical and phase I/II clinical trial data that have been completed or are ongoing.

Ten-Year Trends in Antiemetic Prescribing in Patients Receiving Highly Emetogenic Chemotherapy.

Prevention of chemotherapy-induced nausea and vomiting is essential to preserve quality of life in patients with cancer receiving highly emetogenic chemotherapy (HEC). Recently, new drugs (eg, fosaprepitant, and the newer neurokinin-1 receptor antagonists [NK1RAs] rolapitant and netupitant) and updated antiemetic guidelines have emerged. However, trends in real-world antiemetic use are understudied.

Breast Cancer Survivorship Care Variations Between Adjuvant Chemotherapy Regimens.

Background: Treatment-related toxicity can vary substantially between chemotherapy regimens. In this study we evaluated the frequency of outpatient office visits among a cohort of early stage breast cancer survivors after completion of 4 different adjuvant chemotherapy regimens to better understand how differences in toxicities between regimens might affect health care use.

Materials And Methods: We analyzed administrative claims data from a US commercial insurance database (OptumLabs) to identify women who received adjuvant doxorubicin/cyclophosphamide (AC), AC followed or preceded by docetaxel or paclitaxel (AC-T), AC concurrent with docetaxel or paclitaxel (TAC), or docetaxel/cyclophosphamide (TC) between 2008 and 2014.

Variability of performance status assessment between patients with hematologic malignancies and their physicians.

This study was conducted to determine the incidence of inter-observer variability in Eastern Cooperative Oncology Group (ECOG) performance status (PS) rating between patients with leukemia and lymphoma and their physicians. ECOG PS was assessed at diagnosis by patients and their physicians and stratified by disease subtype, gender, age, disease stage and education. Association between patient- and physician-rated PS and overall survival (OS) was stratified by subtype and prognostic risk score.

BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer.

Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 ( BRAF mutations).

Hormonal and Reproductive Factors and Risk of Myeloproliferative Neoplasms in Postmenopausal Women.

Background: Hormonal and reproductive history has been associated with risk of some hematologic malignancies, but their role in myeloproliferative neoplasms (MPN) is largely unknown.

Methods: Using a population-based cohort study, we evaluated the association of these factors with risk of MPN overall, and for essential thrombocythemia (ET) and polycythemia vera (PV) specifically. Incident MPN cases from 1993 to 2004 were identified via linkage to Medicare.

An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy.

Purpose: Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens.

Widespread use of complementary and alternative medicine among non-Hodgkin lymphoma survivors.

There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. Seven hundred and nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. Altogether 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals.