BRAIN CANCER

HER2-Positive Breast Cancer

BREAST CANCER

Bladder Cancer

Prostate Cancer

Renal Cell Carcinoma

GENITOURINARY CANCERS

Liquid Biopsies

GENOMIC TESTING

Colorectal Cancer

GASTRIC CANCER

GIST

GI CANCERS

Cervical Cancer

ENDOMETRIAL CANCER

Ovarian Cancer

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

BONE MARROW & STEM CELL TRANSPLANT

HEMATOLOGY

CAR T-CELL THERAPY

IMMUNOTHERAPY

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

LEUKEMIAS

MET-TARGETED THERAPY

SMALL CELL LUNG CANCER

BIOMARKER-DRIVEN LUNG CANCER

EGFR+ Lung Cancer

LUNG CANCER

DLBCL

Follicular Lymphoma

Mantle Cell Lymphoma

LYMPHOMAS

MPNs

MULTIPLE MYELOMA

NTRK GENE FUSIONS

SARCOMA

Melanoma

SKIN CANCERS

THYROID CANCERS

NEWS

All News

FDA Briefs

Oncology Icons

Special Reports

Voices from the Field

CONFERENCES

Conference Coverage

Conference Listing

Data Dialogue with the Oncology Brothers

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Pivotal Practice Views with the Oncology Brothers

Podcasts

Precision Medicine

PUBLICATIONS

All Publications

Evolving Paradigms

Peers & Perspectives in Oncology

Targeted Therapies in Oncology

CME/CE

RESOURCES

Case-Based Roundtable Series

Clinical Trials

Partners

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

eNewsletter

Print Subscription

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

Twitter

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Biomarker-Driven Lung Cancer

Bone Marrow & SCT

CAR T-Cell Therapy

EGFR-Positive Lung Cancer

Endometrial Cancer

Lung Cancer

Multiple Myeloma

Small Cell Lung Cancer

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Sarcoma

Skin Cancers

Spotlight

1rem

Clinical

In season 4, episode 1 of Targeted Talks, Benjamin L. Schlechter, MD, senior physician at Dana-Farber Cancer Institute and instructor in Medicine at Harvard Medical School, discuses new studies in the  gastrointestinal cancers space. Schlechter explains how these studies can inform future research.

First, in a phase 1a/1b study (NCT03860272) of botensilimab (AGEN1181) plus balstilimab (AGEN2034), promising clinical activity and durable responses were shown in patients with metastatic heavily pretreated patients with microsatellite stable (MSS) colorectal cancer (CRC). The findings were presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). Schlecter explains that botensilimab is a first-in-class drug targeting the CTLA-4 protein receptor, and therefore offers something different than the anti-CTLA-4 therapies that are currently available.

“I don't think anyone expected things like this to work, because there have been so many failures in this space. I think it emphasizes that this is not just a CTLA-4 inhibitor, and not just a checkpoint inhibitor. There’s something fundamentally different about how this agent behaves. We see that in the efficacy profile and the toxicity profile. And I think it's easy to put this in the same basket as tremelimumab [Imjudo], or ipilimumab [Yervoy], and I don't think that's fair assessment. It's a next class of drug, and it really is its own thing,” Schlechter says.

In another early-phase study (TACTIC-02; NCT04727151), investigators are exploring the use of autologous T cells expressing T-cell antigen couple (TAC) that target HER2 in patients with solid tumors. Schlechter says that T-cell therapy is difficult in solid tumors, but if this study is successful, it will create opportunities for other targeted therapy studies in the future.

Schlechter says: “I think this is a really important beginning. If we can target HER2 safely and successfully, this really opens the door for a number of targets that right now are off limits. There are so many cancers right now that we know there's a target for, but we can't go after that target because there's so much targeting normal tissue that it will be dangerous to do so. This is both an important innovation in T-cell therapy and HER2. But this is also important innovation for cellular therapy in oncology because products like this would allow us to target far more things than we currently can with existing technology.”

Schlechter also discusses later-phase trials that appear to be practice-changing. The SUNLIGHT study (NCT04737187), for example, may have global implications for adding 

bevacizumab (Avastin) to the combination of trifluridine/tipiracil (Lonsurf)

 for the treatment of metastatic CRC. This strategy is already standard in the United States. In addition, adding liposomal irinotecan to 5-fluorouracil with leucovorin plus oxaliplatin (NALIRIFOX) may achieve better efficacy compared with standard treatment, as shown in the 

 in patients with pancreatic ductal adenocarcinoma.

1. El-Khoueiry AB, Fakih M, Gordon MS, et al. Results from a phase 1a/1b study of botensilimab (BOT), a novel innate/adaptive immune activator, plus balstilimab (BAL; anti-PD-1 antibody) in metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC). 

. 2023; 41(suppl 4): LBA8. doi: 10.1200/JCO.2023.41.3_suppl.LBA8

2. Schlechter BL, Olson D, Sailbil S, et al. A phase I/II trial investigating the safety and efficacy of autologous TAC T cells targeting HER2 in relapsed or refractory solid tumors. 

. 2023;41(suppl 4): TPS816. doi: 10.1200/JCO.2023.41.4_suppl

In season 4, episode 1 of Targeted Talks, Benjamin L. Schlechter, MD, discuses new studies in the gastrointestinal cancers space.

Unpacking the Latest Research in Gastrointestinal Cancers

In season 2, episode 2 of Targeted Talks, Cathy Eng, MD, the David H. Johnson Chair in Surgical and Medical Oncology; professor of medicine, hematology and oncology; co-director, GI Oncology at Vanderbilt-Ingram Cancer Center, speaks with Benjamin Weinberg, MD, associate professor of medicine, Division of Hematology and Oncology, in the Lombardi Comprehensive Cancer Center at Georgetown University, about the gut microbiome, and how the presence of certain microbiota impact the onset and intensity of disease as well as the potential response to certain treatments.

In recent years, the increasing number of 

young adults developing colorectal cancer

 has been believed to be closely linked with the gut microbiome. Several studies have examined this onset of disease and suggested that diet and obesity may play a role. Still, there is little known about how the gut microbiome may impact average-aged patients and the older patient population.

Other ongoing questions in the space include how to utilize information obtained from 

gut microbiome research in colorectal cancer

 to diagnose, treat, and monitor disease.

In season 2, episode 2 of Targeted Talks, Cathy Eng, MD, speaks with Benjamin Weinberg, MD, about the gut microbiome, and how the presence of certain microbiota impact the onset and intensity of disease as well as the potential response to certain treatments.

The Impact of the Gut Microbiome in Young Patients With Colorectal Cancer

In an interview, Mohamad Adham Salkeni, MD, FRCPC, discussed the ongoing study of maintenance ivaltinostat plus capecitabine or capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease has not progressed on first-line FOLFIRINOX.


Ivaltinostat Combinations Show Promise for Pancreatic Adenocarcinoma

The Independent Data Safety Monitoring Committee for the phase 2 ASCEND trial has given the okay to continue evaluation of LSTA1 for patients with pancreatic cancer.

Phase 2 ASCEND Trial Will Continue Investigating LSTA1 in mPDAC

During a Targeted Oncology™ Case-Based Roundtable™ event, David Zhen, MD, explored treatment options for patients with advanced HER2-negative upper gastrointestinal cancers. 

Zhen Explores the Role of  Immunotherapy in Upper GI Cancers

Immune checkpoint inhibitors are approved for dMMR/MSI-H gastrointestinal cancer treatment; however, approximately half of patients with dMMR/MSI-H gastrointestinal cancer exhibit primary resistance to them.

Overcoming Resistance in Gastrointestinal Cancers

Based on the largest clinical trial of patients with HER2-amplified biliary tract cancer, a novel anti-HER bispecific antibody may be the next option.

Zanidatamab Shows Potential to Enter the Armamentarium for HER2+ BTC

Roby Thomas, MD, a medical oncologist, and hematologist at UPMC Hillman Cancer Center, discusses chemotherapy shortages and the impact these shortages have had on oncology research.

Thomas explains that an important agent for the treatment of gastrointestinal and genitourinary oncology is 

. The chemotherapeutic is standard treatment for pancreatic cancer, breast cancer, and non–small cell lung cancer. Nab-paclitaxel is also being investigated in studies of patients with gastric cancer, and breast cancer with brain metastases. Thomas explains that continuing these studies was a big challenge back when there was a shortage of nab-paclitaxel

Many oncologists used the combination of leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) in place of nab-paclitaxel, says Thomas. FOLFIRINOX is the only alternative treatment for these patients, but for older patients, it may be too toxic.

Other necessary agents include gemcitabine and cisplatin, which are currently short of supply.

 We've had multiple issues with drug shortages over the last couple of years, primarily because of supply chain issues. In the fields that I focus on, gastrointestinal and genitourinary oncology, we had a shortage of nab-paclitaxel for quite some time, and that was in the United States. What made it so challenging is we use that drug often in pancreatic cancers. At UPMC Hillman Cancer Center, we have a high volume of pancreatic cancers, and it's 1 of our standard-of-care therapies.

 What made it uniquely challenging for us was that we have many different phase 1 and phase 2 clinical trials in which nab-paclitaxel would be part of a standard-of-care regimen. People might be randomized to get gemcitabine and nab-paclitaxel with or without another study drug or placebo, for example, but we couldn't recruit people because we just didn't have the study medication. It did not just have a direct effect in terms of less nab-paclitaxel availability, but also in terms of accrual and clinical trials. It was a challenging time for pancreatic cancer in general.

Videos

Roby Thomas, MD discusses chemotherapy shortages and the impact these shortages have had on oncology research.

Chemotherapy Shortages Trouble Study Investigators

Tara Seery, MD, a physician at the Hoag Cancer Center, discussed the next steps for the novel treatment of combination immunotherapy protocol of low-dose chemoradiation, N-803, and PD-L1 t-haNK therapy, for patients with metastatic pancreatic cancer center.

Use of this combination was looked at in the multi-center, randomized, phase 2 QUILT 88 study (NCT03563144) that gave patients 100 mg/m2 via IV infusion chemoradiation nab-paclitaxel, 600 mg/m2 IV of gemcitabine, twice daily cyclophosphamide at 50 mg, and low dose stereotactic body radiation therapy. Seery explains that this method is to address that treatment with just chemotherapy may not be enough in this patient population.

2023 ASCO Gastrointestinal Cancers Symposium

, which showed median overall survival (OS) at 5.7 months (95% CI, 4.9-6.4) with 37% of patients having achieved stable disease at 8 weeks or longer. Median OS in the third-line setting, which included 38 patients, was 6.3 months, whereas 40 patients in the fourth line setting had a median OS of 5.0 months.

Seery also explains what these results mean for the future of this treatment and where she believes this treatment combination can benefit this patient population.

We still have an ongoing second-line trial. So, when we opened the third line, people from all over the world flocked in. Now that that is full, we really want to get the second-line filled. So second-line is for patients who have had only 1 prior line of therapy, and we are randomizing patients 50/50 to either our experimental arm vs what is approved as our standard of care 5-FU and irinotecan liposome injection [Onivyde].

Now, we know that might be a little issue with [the irinotecan liposome injection] in the first-line setting, but still, 50% of patients receive first-line gemcitabine [and paclitaxel]. Some people might say they had gemcitabine and [paclitaxel], so why would they want to go into this experimental arm that does use gemcitabine and [paclitaxel]. We have seen people respond even if they've received gemcitabine and [paclitaxel] before, so that's not an issue in our minds.

Tara Seery, MD, explains the next steps for the QUILT 88 study looking at a novel combination of therapies for patients with metastatic pancreatic cancer.

Next Steps for Novel Treatment Combination in Pancreatic Cancer

Ken Kato, MD, PhD, chief of the department of head and neck, and esophageal medical oncology and gastrointestinal medical oncology at the National Cancer Center Hospital in Tokyo, Japan, discusses the traits clinicians should look out for when seeing if a patient with esophageal squamous cell carcinoma (ESCC) is a candidate for the combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

Based on updated findings of the phase 3 CheckMate 648 trial (NCT03143153) that were presented at the 

, at a median follow-up of 28.8 months, the median overall survival (OS) for patients on nivolumab and chemotherapy (n = 321) was 12.8 months (95% CI, 11.1-15.7) vs 10.7 months (95% CI, 9.4-12.1) for patients on chemotherapy alone (n = 324). The 24-month OS rate also favored the combination vs chemotherapy alone at 29% vs 19%, respectively. For patients with a PD-L1 expression of 1% or higher, the median OS still favored the nivolumab combination arm at 15 months compared with 9.1 months in the chemotherapy arm (HR, 0.59; 95% CI, 0.46-0.76).

OS was significantly longer for patients with a PD-L1 expression of 1% or greater on ipilimumab/nivolumab compared with those on chemotherapy alone at a median of 13.7 vs 9.1 months, respectively (HR 0.64; 98.6% CI, 0.46-0.90; 

 = .001). Moreover, this result was also seen in the overall population of patients on ipilimumab/nivolumab compared with patients on chemotherapy alone at 12.7 vs. 10.7 months (HR, 0.78; 98.2% CI, 0.62 to 0.98; 

 = .01). These results were based on a preliminary analysis of the CheckMate 648 trial that Kato presented at last year’s ASCO GI Symposium, but according to Kato, they have continued to hold true in real world data.

Here, Kato discusses which patient profiles fit the best for use of the immunotherapy combination over chemotherapy alone in patients with an acceptable ECOG performance score and a strong PD-L1 positivity score. 

We found the better response with [ipilimumab and nivolumab] and with longer follow-up, compared with the chemotherapy/nivolumab. We should focus on the patient who achieved a long-term efficacy [result] with ipilimumab and nivolumab.

Last year, [we] presented [that for the] patient, [there is] already a benefit with ipilimumab/nivolumab. I think that the patient with a less aggressive disease with a small tumor burden, a good performance status, and good nutritional status, can be a good candidate for the ipilimumab/nivolumab treatment. Of course, the PD-L1 positivity is good and the predictive marker for the ipilimumab/nivolumab treatment, which we already [have seen] in the real-world data with ipilimumab/nivolumab and the patient background in the further evaluation.

Ken Kato, MD, PhD, discusses which patient characteristics to look out for when looking to put a patient on the combination of ipilimumab and nivolumab.

News

Discussing Patient Characteristics in ESCC On Ipilimumab/Nivolumab

Jashodeep Datta, MD, a surgical oncologist at Sylvester Comprehensive Cancer Center and assistant professor of Clinical at the University of Miami Miller School of Medicine, explains 

 co-alteration in patients with pancreatic cancer.

, explains Datta. The reason for these co-alterations is unknown, and oncologists also do not have a clear picture of how this effects the disease. These questions were explored preclinically and warrant further study.

 We are very interested in understanding the chasm that exists between the genotype of pancreas cancer and the virulent phenotype of pancreas cancer. What makes it so hostile for patients? To do that we approach this from the genome of the pancreatic cancer cell, which is really the incipient event in pancreatic tumorigenesis. And what's very interesting about pancreas cancer is compared with all of the cancers, if you look across the Cancer Genome Atlas, pancreatic cancer is the number one cancer that has cooperated mutations of 

 We really want to understand if there is a biologic basis for that, and what are the downstream repercussions of that. The was really the basis of this study. The most important finding that really paved the way for the remainder of our study was our finding, using a cohort of 250 patients from the University of Miami, as well as validation in two independent datasets, one from the Cancer Genome Atlas, as well as one from an international molecularly annotated data set the ICGC, where we showed that patients who had quadrate mutations in 

 had worse survival and worse prognosis compared with patients who had mutations in either the carrier s gene alone. And they had may have other mutations, but not 

. So, this really paved the foundation for the remainder of the study.

Jashodeep Datta, MD, explains KRAS and TP53 co-alterations in patients with pancreatic cancer.

Investigating KRAS/TP53 Co-Alterations in Pancreatic Cancer

Zev A. Wainberg, MD, a professor of medicine at University of California, Los Angeles, and co-director of the UCLA GI Oncology Program, discusses the recent findings from NAPOLI 3 (NCT04083235) which were presented at the 2023 Gastrointestinal Cancers Symposium.

The randomized, open-label, pivotal phase 3 NAPOLI 3 trials is evaluating the combination of irinotecan liposome injection (Onivyde), 5-fluorouracil (5-FU), oxaliplatin, and leucovorin (NALIRIFOX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Patients enrolled in the study were required to be diagnosed 6 or less weeks prior to screening, have at least 1 metastatic lesion measurable by MRI or CT scan per RECIST v1.1 criteria, and have an ECOG performance status of 0 or 1.

Recent findings revealed that treatment with NALIRIFOX improved overall survival and progression-free survival compared with nab-paclitaxel plus gemcitabine in this patient population of previously untreated patients with mPDAC.

 We presented the top-line results, which included the overall survival, which was statistically significantly improved in the group of patients who've got NALIRIFOX over nab-paclitaxel plus gemcitabine by about 2 months. The median improvement was about 2 months, the hazard ratio is .83, and the 

 value is .04. The statistics also showed that this progression-free survival was superior with NALIRIFOX over nab-paclitaxel plus gemcitabine. There was no statistically significant difference in response rate, although the response rate was numerically higher with NALIRIFOX, but it did not make statistical significance.

 The safety of the regimens essentially is a tradeoff, in my opinion, of toxicity between 1 regimen that causes more of the GI toxicity that have been influenced at higher rates of diarrhea and nausea, as opposed to higher rates of cytopenias, which are neutropenia, anemia and thrombocytopenia. Those were seen more commonly in the nab-paclitaxel plus gemcitabine arm. It is a tradeoff of toxicity profiles when one talks to their patients.

Zev A. Wainberg, MD, discusses recent findings from the NAPOLI 3 trial which were presented at the 2023 Gastrointestinal Cancers Symposium.


GI CANCERS

Latest News