Reporter: Sarah Maxwell

BARCELONA—Pembrolizumab did not significantly improve overall survival (OS) or progression free survival (PFS) compared with paclitaxel as second-line therapy in patients with advanced gastric or gastro-esophageal junction cancer that had progressed after one line of chemotherapy (containing a platinum and fluoropyrimidine) in the KEYNOTE-061 randomized open-label controlled phase three trial reported at the ESMO 20th World Congress on Gastrointestinal Cancer. https://www.ncbi.nlm.nih.gov/pubmed/29880231.

Molecular Biomarker

The lack of statistical benefit was despite the fact that the analysis was with patientswho had been selected because they had programmed cell death ligand 1 (PD-L1) combined positive scores (CPS) of 1 or higher—indicating at least a one per cent positive staining rate in their tumors—marking them as theoretically ideal candidates for therapy with this checkpoint inhibitor antibody that targets programmed cell death 1 (PD-1) molecular features.

The findings call into question the simplistic concept that targeting a molecular feature on a particular tumor will necessarily be sufficient to work as a method of treating that cancer.

Sub-Groups

But lead author Kohei Shitara MD, Chief Doctor in the gastrointestinal department of the National Cancer Center Hospital East in Kashiwa, Japan, said that sub-group analysis yielded positive findings for some patients and that pembrolizumab had a better safety profile than paclitaxel.

He tells the Audio Journal of Oncology: “The trial did not meet the primary endpoints to show survival improvement [or] PFS improvement,” he said. But some of the patients showed “very durable benefit” with pembrolizumab. The sub-group study confirmed that patients with good performance status and having at least 10 per cent staining for PD-L1 expression (defined as a CPS score of 10) had improved prospects—as did those with tumors expressing high microsatellite instability (MSI).

BARCELONA—Oral cabozantinib “significantly improved” overall survival (OS) and progression free survival (PFS) compared to placebo in patients with advanced hepatocellular carcinoma(HCC) whose disease had progressed despite sorafenib therapy in the phase 3 CELESTIAL trial reported to the 2018 ESMO World Congress on Gastrointesinal Cancer.

http://ascopubs.org/doi/abs/10.1200/JCO.2018.36.4_suppl.207

“This is a new oral drug [that’s] very easy for the patient to take at home. And it works for some patients.  When it works it can work very well. It can prolong life—and with very good responses in some patients in terms of tumor necrosis, tumor shrinkage, tumor de-vascularization.  It’s well tolerated and it’s a new tool to fight against cancer,” according to study co-author Philippe Merle MD PhD, a hepato-gastro oncologist and medical oncologist at the Hospice Civile de Lyon University Hospital in Lyon, France. He discusses the CELESTIAL trial and it’s clinical implications with the Audio Journal of Oncology’s Sarah Maxwell.

BARCELONA—A chemotherapy combination consisting of trifluridine with tipiracil showed a “clinically meaningful and statistically significant” improvement in overall survival (OS) and progression free survival (PFS) compared with placebo in patients with heavily-pretreated metastatic gastric cancer (mGC) refractory to standard therapies in the randomized phase three TAGS study reported at the ESMO 20th World Congress on Gastrointestinal Cancer. https://academic.oup.com/annonc/article/29/suppl_5/mdy208.001/5043314

“The TAGS study has shown in a randomized phase three setting that trifluridine-tipiracil is an available option for treating patients with gastric or gastro-esoophageal cancer in the metastatic refractory setting,” said lead author Josep Tabernero MD PhD, Chair of Medical Oncology at Vall d’Hebron University Hospital in Barcelona, Spain in this edition of the Audio Journal of Oncology.

Patients lived a median of 5.7 months when treated with the new combination compared with 3.6 months in the control group receiving best supportive care—a 2.1 months extension of life and a 31 per cent reduction in the risk of death (hazard ratio: 0.69).

Professor David Cunningham MD FRCP, Consultant Medical Oncologist and Director of Clinical Research at the Royal Marsden Hospital, London  adds his comments about the role of this combination in gastric cancer in the clinic.

CHICAGO—A 25 per cent risk reduction for esophageal cancer was found to be associated with prophylactic therapy consisting of a proton pump inhibitor (PPI) and aspirin in the phase three randomized ASPECT multicenter study from the United Kingdom reported at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The trial investigated long-term daily high doses of esomeprazole (80 mg or 20 mg daily) together with aspirin (300 mg) among 2563 patients who had Barrett’s Esophagus (BE) and were therefore at high risk of the disease.

Although the study focused on people with Barrett’s Esophagus, lead study author Janusz Jankowski, MD, PhD, Deputy Vice Chancellor, Royal College of Surgeons, Ireland and Consultant Clinical Adviser, National Institute for Health and Care Excellence, UK told the Audio Journal of Oncology he believed that any person with heartburn could consider taking a high-dose proton pump inhibitor and aspirin after speaking with their doctor.  But he warned that patients should not self-medicate since the benefits so far had been found in the specific subset of patients who had BE.

CHICAGO—Patients with resectable and “borderline resectable” pancreatic cancers treated with chemoradiation before surgery (followed by adjuvant chemotherapy) had significantly improved outcomes compared to those randomized to have surgery first and adjuvant chemotherapy in the Dutch Pancreatic Cancer Group’sPREOPANC-1 randomized, controlled, multicenter phase III trialreported at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO).

https://meetinglibrary.asco.org/record/160063/abstract

Although fewer tumors could be resected in patients treated with preoperative therapy compared with those on standard care (down from 72 to 62 per cent) there was a markedly increased rate of complete resections, said study author Geertjan Van Tienhoven MD, PhD, a radiation oncologist at the Academic Medical Center in Amsterdam, Netherlands, who is a member of the Dutch Pancreatic Cancer Group. He discusses the PREOPANC-1 study implications with the Audio Journal of Oncology.

CHICAGO—Clinically targetable mutations were identified and patient subgroups pinpointed by whole genome sampling (WGS) of castration-resistant metastatic prostate cancer (mPC) in a study reportedatthe 2018 Annual Meeting of the American Society of Clinical Oncology. (https://meetinglibrary.asco.org/record/160671/abstract)

Lisanne F van Dessel MD, a medical oncologist at Erasmus Medical Center Cancer Institute in Rotterdam, The Netherlands, tells the Audio Journal of Onclogy that while their research confirmed that this disease was complex and unstable they had found potentially actionable targets waiting to be studied for therapeutic use which were also likely to be prognostic, predictive or both.

CHICAGO—A gene test that predicts for relapse in women with estrogen receptor positive early breast cancer can identify patients with low-risk disease who could safely avoid extending their endocrine therapy beyond the standard five years, according to study findings reported in a poster session at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Co-author Graham M Poage PhD, a scientist with the Biotheranostics Company based in La Jolla, California tells the Audio Journal of Oncology about the “Breast Cancer Index” (BCI) test—a reverse transcription polymerase chain reaction (RT-PCR) 11-gene assay—was an endocrine-therapy decision-making tool that had identified very low risk—patients who had 20-year breast cancer specific survival of 98 per cent—a significant proportion of patients who, potentially, could be spared extended endocrine therapy because their risk is so low that continued therapy is unlikely to benefit [them].

CHICAGO—Men who had breast-conserving therapy (BCT) including radiation for their early breast cancer lived longer than those who had total or partial mastectomy—with or without radiation—in findings from a large retrospective survey of male breast cancer reported at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO).

https://meetinglibrary.asco.org/record/162945/abstract

In a poster presentation at ASCO Sarah Bateni MD, a surgery resident at the University of California Davis Medical Center in Sacramento, reported survival outcomes from an analysis of National Cancer Database (NCDB) records of 11,406 men who had stage one, two or three breast cancer between the years 2004 and 2015. She discusses the findings with the Audio Journal of Oncology in the company of her colleague, Candice A. M. Sauder, MD, MEd, a Breast Surgical Oncologist at University of California Davis Medical Center.

CHICAGO—Women and men were treated differently for the same tumor stages of head and neck cancer (HNC) and had different outcomes in a study with patients surveyed over a fifteen-year period in Santa Clara, California. The findings—using the generalized competing event (GCE) assessment model that balanced the risk of cancer death against non-cancer death—has prompted a call to reassess the influence of gender on treatment decision-making.

Study author Jed A. Katzel MD, a medical oncologist with Kaiser Permanente in Santa Clara, talks with the Audio Journal of Onclogy about his new data from GCE modeling he reported at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).

(Abstract LBA6002: Are women with head and neck cancer undertreated?)

https://meetinglibrary.asco.org/record/161984/abstract

Commenting on the findings ASCO Expert Joshua A Jones, MD MA, a radiation oncologist at the Perelman School of Medicine at University of Pennsylvania in Philadelphia said: “We don’t know why women are getting less treatment and having worse outcomes and we need to find out. Though these findings are specific to California the disparities we see are startling and worth considering in treatment discussions in everyday practice.”

CHICAGO, IL—Patients whose non-small cell lung cancers (NSCLC) expressed more than one per cent of the programmed death ligand-1 (PD-L1) tumor proportion score (TPS) lived longer when treated with the anti programmed death 1 (PD-1) antibody pembrolizumab than a control group of patients receiving platinum-based chemotherapy in the open-label, phase three KEYNOTE-042 study reported at the American Society of Clinical Oncology (ASCO) annual meeting plenary session.  https://meetinglibrary.asco.org/record/165950/abstract

Better survival

Principal author of the study, Gilberto Lopes MD, Associate Professor of Clinical Medicine at the University of Miami’s Sylvester Comprehensive Cancer Center tells the Audio Journal of Onclogy patients treated with pebrolizumab monotherapy lived a median of four to eight months longer than those who received chemotherapy and had fewer severe side effects than with chemotherapy (18 per cent as compared with 41 per cent).