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Accreditation/ Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit™.

Acknowledgment of Commercial Support

This activity is supported by educational grants from Bayer HealthCare Pharmaceuticals Inc., Celgene Corporation, Lilly, Merck Sharp & Dohme Corp., Sirtex Medical Inc., and Taiho Oncology.

For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.


Community Practice Connections™: 2nd Annual School of Gastrointestinal Oncology™ PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


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PER Pulse™ Recap

Immune Therapy in Gastrointestinal Cancers

The 2nd Annual School of Gastrointestinal Oncology (SOGO), which was held April 29, 2017, presented the latest data on the multidisciplinary management of patients with gastrointestinal (GI) cancers, including colorectal cancer (CRC), gastric cancer, pancreatic cancer, and hepatocellular carcinoma, among others. This first of 3 PER® Pulse Recaps from the SOGO meeting centers on the emerging use of immune therapy in GI cancers.

John Marshall, MD, Chief of the Division of Hematology/Oncology at Georgetown University Hospital, Washington, DC, focused his presentation, “Fighting a Smarter War on Colon Cancer: Immune Therapy in GI Cancers,” primarily on the use of immune checkpoint inhibitors, both in metastatic CRC (mCRC) and advanced gastric cancer.

He presented a study by Dr. Dung Le showing that, among CRC tumors deficient in mismatch repair (dMMR), immune checkpoint inhibition with pembrolizumab was highly active, with a 62% response rate and strikingly improved overall survival (OS) and progression-free survival (PFS) compared with MMR-proficient (pMMR) tumors. Similarly, favorable results were also observed with dMMR-non‒CRC tumors. Dr. Marshall also presented interim results from the CheckMate-142 trial of nivolumab plus/minus ipilimumab in patients with mCRC with microsatellite instability-high (MSI-H) tumors, which is a surrogate of MMR deficiency. In this study, nivolumab alone or in combination with ipilimumab demonstrated activity, with an apparent improvement with combination therapy. However, the combination arm also produced increased toxicity compared with the single-agent arm.

Dr. Marshall also presented a phase III, placebo-controlled trial of nivolumab in advanced gastric cancer. In this trial of heavily pretreated patients, nivolumab demonstrated a significant improvement in response rate, OS, and PFS, leading to approval of this agent in gastric cancer. In particular, he pointed out that the PFS Kaplan-Meier curve was suggestive of a subset of patients for whom nivolumab was active, which led to his assertion that patients with gastric cancer should also be tested for MSI status.
He then moved on to discuss ways in which MSI is tested, described the confusion surrounding it, and contrasted MSI testing with tumor mutation burden (TMB) testing. Tumor mutation burden and MSI are directly correlated with one another in CRC and gastric cancers, and TMB testing is less complex, requiring only next-generation sequencing. Neither PD-1 nor PD-L1 expression are correlated with TMB.

Finally, Dr. Marshall discussed 2 clinical trials combining immunotherapy with another partner. The first was a phase III trial of a PD-L1 inhibitor (atezolizumab) and a MEK inhibitor (cobimetinib) in microsatellite-stable (MSS) CRC tumors. The results of this trial, which has finished accrual, are highly anticipated because the MSS subset of patients is generally considered nonimmunogenic. The second combination therapy trial was a phase I/II trial of a carcinoembryonic antigen (CEA) vaccine combined with the PD-L1 inhibitor durvalumab in mCRC or pancreatic adenocarcinoma. This trial was designed after the CEA vaccine alone showed a better-than-expected OS in patients with stage IV CRC with no evidence of disease.

For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 2nd Annual School of Gastrointestinal Oncology, as well as downloadable slides summarizing results from the meeting.


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PER Pulse™ Recap

Recent Advances in Treatment of Hepatocellular Carcinoma: Immunotherapies vs TKIs

The 2nd Annual School of Gastrointestinal Oncology (SOGO), which was held April 29, 2017, presented the latest data on the multidisciplinary management of patients with gastrointestinal cancers, including colorectal cancer, gastric cancer, pancreatic cancer, and hepatocellular carcinoma (HCC), among others. This second of 3 PER® Pulse Recaps from the SOGO meeting centers on existing and emerging therapies (tyrosine kinase inhibitors [TKIs] and immune checkpoint inhibitors) for HCC.

Aiwu Ruth He, MD, PhD, associate professor of Medicine at Georgetown University, Washington, DC, used her presentation, “Clash of the Titans in Hepatocellular Carcinoma: Immunotherapies vs TKIs,” to discuss the most recent data from these 2 approaches. First, she discussed how the success of sorafenib in HCC was followed by the failure of many other TKIs to show a benefit in HCC, until regorafenib was able to demonstrate significant benefit in the second-line HCC setting in the RESORCE trial. She described the efficacy and safety results of this trial of patients who had progressed on sorafenib, including the 2.8-month improvement in overall survival (OS), which was the primary endpoint of the trial. This survival benefit was seen across virtually all subtypes, and a significant progression-free survival (PFS) benefit was present as well. The safety profile of regorafenib was manageable and consistent with the known safety profile of this agent.

Dr. He then introduced evidence showing why HCC is immunosuppressive, such as the elevated production of immunosuppressive cytokines and impaired function of antigen-presenting cells. She presented data from CheckMate-040, a phase I/II dose-escalation trial with an expansion phase of nivolumab in advanced HCC, stratified by hepatitis C virus (HCV) and hepatitis B virus (HBV) infection status. Nivolumab responses were present in all 4 cohorts – the HCV cohort, the HBV cohort, and the 2 uninfected cohorts stratified by previous sorafenib status (sorafenib progressors and sorafenib-naïve/intolerant). Responses appear durable, with median duration of response not yet reached, and 9-month survival rates across cohorts already exceeding the historical median survival of 8 months for patients who progress on sorafenib.
Dr. He finished her lecture by summarizing the state of therapy for HCC, and presenting needs for future investigations. Specifically, the sequence of using TKIs and immunotherapy needs to be examined, as does the investigation of both biomarker development and combination therapies using immunotherapy in HCC. She also stated that more information regarding the safety experiences of patients with moderate liver dysfunction was needed.

For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 2nd Annual School of Gastrointestinal Oncology, as well as downloadable slides summarizing results from the meeting.


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PER Pulse™ Recap

Management of Advanced Colorectal Cancer in 2017

The 2nd Annual School of Gastrointestinal Oncology (SOGO), which was held April 29, 2017, presented the latest data on the multidisciplinary management of patients with gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer, pancreatic cancer, and hepatocellular carcinoma, among others. This third of 3 PER® Pulse Recaps from the SOGO meeting centers on the management of advanced CRC in 2017.

Cathy Eng, MD, FACP, professor and Director of the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, Houston, focused her presentation, “2017: Update in the Management of Advanced Colorectal Cancer,” on several main ideas, as described below.

CRC Tumor Sidedness
Dr. Eng presented data from the Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) 80405 trial, in which patients with untreated, advanced, RAS wild-type CRC were randomized to treatment with chemotherapy plus bevacizumab or chemotherapy plus cetuximab. The primary endpoint of overall survival (OS) was not significantly different between arms until the data were analyzed by tumor sidedness, when it was discovered that patients with right-sided tumors fared significantly worse overall than those with left-sided tumors (19.4 mo vs 33.3 mo; P <.0001). Moreover, this result was magnified in the cetuximab arm (16.7 mo vs 36.0 mo; P <.0001), leading the National Comprehensive Cancer Network to modify the CRC guidelines to specify that chemotherapy plus EGFR-directed therapy should be restricted to patients with KRAS/NRAS wild-type, left-sided tumors only.

Microsatellite Instability
Dr. Eng presented results from the phase II Le study of patients with progressive, metastatic CRC (mCRC), in which pembrolizumab alone had activity restricted to those patients with microsatellite instability-high (MSI-H) tumors (defined as mismatch repair-deficient), leading to a significant improvement in that patient population in both progression-free survival (PFS) and OS when compared with MSI-stable (MSS) tumors. In the single-arm, phase II CheckMate-142 trial in patients with MSI-H, recurrent mCRC, the PD-1 inhibitor nivolumab showed a 32.1% response rate and activity regardless of PD-L1 expression, BRAF status, and clinical history of Lynch syndrome. This trial led to the development of the upcoming phase III trial in patients with MSI-H tumors, which will randomize them to chemotherapy plus bevacizumab, atezolizumab alone, or chemotherapy plus bevacizumab plus atezolizumab.

Dr. Eng also presented a phase Ib trial in patients with MSS disease, in which 2 agents that were shown to have little to no single-agent activity in this population—MEK inhibitor cobimetinib and atezolizumab—demonstrated a 17% response rate. These positive results have led to the development of the ongoing phase III COTEZO trial of this combination compared with atezolizumab alone or regorafenib alone in patients with unresectable mCRC.

BRAF Mutations
Dr. Eng discussed recent studies on patients with BRAF mutations, which are associated with a poor prognosis. In the randomized, phase II SWOG S1406 study, the BRAF inhibitor vemurafenib was added to irinotecan and cetuximab in BRAF-mutated, recurrent mCRC. The addition of vemurafenib produced a significant increase in median PFS, the primary endpoint (4.4 mo vs 2.0 mo; P =.0002), and in disease control rate (67% vs 22%; P =.001). Because of these positive results, a phase III study of vemurafenib as a part of combination therapy is in development.

HER2-Positive Disease
HER2-positive (HER2+) disease accounts for <5% of all CRC cases. Based on preclinical data showing that HER2 amplification is a driver of resistance to cetuximab, and that HER2+ disease is sensitive to dual HER2 blockade, the HERACLES trial was conducted to test the safety and activity of trastuzumab plus lapatinib in patients with HER2+, KRAS wild-type mCRC. Despite the fact that this patient population was heavily pretreated, the response rate was 34.7%. The positive results from this trial have led to the design of the upcoming SWOG 1613 trial, in which patients with HER2+ disease will be treated with the HER2 inhibitors trastuzumab plus pertuzumab.

For additional commentary about these topics and others, visit www.gotoper.com for archived video of the 2nd Annual School of Gastrointestinal Oncology, as well as downloadable slides summarizing results from the meeting.





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