Sara Karlovitch

In patients with advanced, heavily pretreated biliary tract solid tumors, Stivarga (regorafenib) plus Bavencio (avelumab) had minor anti-tumor activity, according to data from a cohort of patients enrolled in a phase 2 trial.

The study results, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, also demonstrated that certain subgroups of patients were found to have a higher chance of deriving benefit from the combination, warranting further research.

Patients with advanced-stage biliary tract cancer (BTC), tend to have a poor prognosis with no available treatment option after failure of first-line treatment with cisplatin/gemcitabine chemotherapy. Immune checkpoint inhibitors alone have only shown modest results. However, research suggests that targeting vascular endothelial growth factor (VEGF) and its receptor (VEGFR) may help immune checkpoint inhibition in this patient population.

Thirty-four patients were enrolled onto the REGOMUNE study, and 33 were eligible to receive treatment. All patients were evaluated for safety and 29 were evaluated for how effective the drug regimen was at attacking cancer. The patients included in the cohort were highly functioning, had measurable disease, and had one or more previous lines of systemic treatment.

The primary endpoint for the BTC group was the six-month objective response rate (ORR), defined as how much patients’ tumors shrunk. Secondary endpoints include best overall response (the percentage of patients whose cancer responds to and shrinks from treatment), six-moth progression-free rate, progression-free survival (PFS; how long patients live without their disease getting worse), overall survival (OS) and safety.

The cohort received Stivarga at 160 mg/day for three weeks with one week off. Patients also received Bavencio at 10 mg/kg intravenously on day 15 of the first 28-day cycle and then once every two weeks. Treatment was continued until disease progression.

Of the patients enrolled, one patient did not receive treatment as they did not meet the eligibility criteria since they received previous treatment less than three weeks before treatment initiation. No patients were lost to follow-up. Twenty-eight patients discontinued intervention, 26 due to disease progression, one due to death and one due to general/specific change in the patient condition.

More than 52% of the cohort was male, and 50% had an ECOG status (which measures how functional a patient is) of 1. The majority of patients (76.5%) had intra-hepatic tumor location, 20.6% had extra-haptic tumor location and 2.9% had gallbladder tumor location.

Additionally, 82.4% had multiple metastatic sites, the majority of which (79.4%) were in the liver. Other metastatic sites included the lungs (58.8%), peritoneum (41.2%), lymph node (52.9%), and other (32.4%). All patients received platinum-based and gemcitabine-based chemotherapy. Additionally, 38.2% received topoisomerase 1 or 2 inhibitors, and 8.8% received taxanes. The most common number of prior treatment lines was one (41.2%), but 35.3% of patients received two prior lines of treatment and 23.5% received more than two prior lines of treatment.

Objective responses were determined by the percentages of complete responses (CRs), partial responses (PRs), stable disease (SD), and progressive disease (PD) observed by imaging tumor assessment. No patients in the cohort achieved a CR. PRs were seen in 13.8% of patients, SD was seen in 37.9% of patients, and progressive disease in 48.3% of patients.

At a median follow-up of 9.8 months, the average PFS was 2.5 months, and the average OS was 11.9 months. Of the 34 patients, 10 patients (34.5%) had tumor shrinkage.

All patients experienced at least one side effect and 85% experienced a severe (grade 3 or 4) side effect. Serious side effects were observed in 62% of patients and 18% of patients withdrew from treatment due to side effects. An additional 18% of patients withdrew from Stivarga due to side effects and 3% withdrew from Bavencio due to side effects. No treatment-related deaths were observed.

Fatigue was the most common mild or moderate side effect, occurring in 65% of patients. Serious or severe fatigue was seen in 15% of patients. Hypertension was the most common serious or severe side effect and was observed in 18% of patients. Mild to moderate hypertension was observed in 18% of patients. Other mild to moderate, and serious or severe side effects included hand-foot syndrome (41%, 9%), alkaline phosphatase and/or gamma-glutamyl transferase increase (21%, 9%), thrombocytopenia (21%, 9%) and maculopapular rash (15%, 12%).

In an exploratory analysis, investigators sought to show how Bavencio plus Stivarga impacted the tumor microenvironment and to find predictive biomarkers of response. Baseline tumor samples were available for 27 patients out of 34, and C2D1 samples were available for eight.

The analysis showed that high PD-L1 expression correlated with a better durable clinical benefit rate and PFS. For patients with high PD-L1 expression, the PFS was 46.15% versus 7.14% in those with low PD-L1 expression at baseline. For patients with high PD-L1 expression, the average PFS was 5.45 months versus 2.8 months in those with low expression.

In addition to PD-L1 expression, better PFS and improved clinical response benefit was linked to having high expression of indoleamine 2,3 dioxygenase 1 (IDO1). The PFS for this population was 5.78 months compared with 1.91 months for those with low IDO1 expression. For patients with high expression of IDO1, the clinical benefit rate was 85.7% versus 7.14% for those with low 1DO1 expression. Further studies, according to the study authors, should evaluate this connection.

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Treatment with the combination of Stivarga and Bavencio was associated with minor anti-tumor activity in patients with advanced, heavily pretreated biliary tract solid tumors.

Two-Drug Combo Shows Modest Benefit in Biliary Tract Cancer

Gastrointestinal (GI) cancers remain a serious issue and places a major burden on both the patient and their caregiver.

As part of the GI Cancers Alliance (GICA), formed in 2015, the Raymond Foundation aims to help people with GI cancers by providing them and their caregivers with support.

sat down with Martha Raymond, executive director of GICA and founder of the Raymond Foundation, at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the organization and resources available for caregivers.

: Can you provide a brief history of the Raymond Foundation? 

 The Raymond Foundation was founded over 30 years ago in honor of my parents, Margaret and Patrick Raymond, who both passed away from colon cancer when they were very young. And back when they were diagnosed, there were not diagnostic tests, there were not screening tests and there was really only one drug available at the time for patients, which was Fluorouracil (5-FU). So, we’ve come a long way in these 30 years with new treatment protocols for patients. And I’m very proud to say that, looking back to where we were 30 years ago to where we are now, we’ve made great strides. I know there are a lot of strides we still need to make to help patients, but again, just in my lifetime. There were not resources back then for patients, even patients (with cancer) in general, much less patients with colon cancer. So, we are looking forward to new growth and opportunities to help both the caregiver and the patient.

What are the new cancer care initiatives? 

We’re very proud of the Raymond Foundation to have launched the first caregiver action plan. And what that is, it’s really a roadmap for cancer caregivers for all disease states to let them know basically, they are not alone and let them know the tools they might use to help them. Because, as we all know, being a caregiver is very difficult because they want to be strong for the patient, but at the same time they need to take care of their own needs, which is very difficult for care givers.

What we provide is information, both on our website and in a downloadable form, so that caregivers will have an actual tool kit, an actual guide to let them know they’re not alone, let them hear stories from other caregivers, what they’ve experienced, that they might learn from lessons from other caregivers. And we’re excited as we continue the launch of our action plan that we’ll go into In-depth programing for newly diagnosed patients, all the way through palliative care and even into a hospice care situation. So, I think we will provide caregivers and patients you know a road map through the whole care continuum.

Can you expand a little on the cancer caregiver action plan? 

Our cancer caregiver action plan is available for free. It is on our website at theraymondfoundation.org and also available in print copies if individuals want to take the actual copy to their oncologist's office, share it with a patient, or even share it in support groups. We’ve learned a lot that caregivers are taking the plan, they’re sharing it, they’re learning from it. And one of the wonderful parts, I think, of the care plan is that it provides a journal as well. So that caregivers can really journal their experience and keep notes about the care continuum with the patient.

Lifting the Burden: How the Raymond Foundation Helps to Support Caregivers

The discovery of one’s hereditary risk for cancer can be scary and challenging; and with numerous myths and misconceptions surrounding genetic mutations, finding accurate information can be hard.

Facing our Risk of Cancer Empowered (FORCE), established by breast cancer survivor and BRCA2 carrier Sue Friedman, helps individuals find accurate information and feel less alone, connecting them to support networks and specialists. At the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Friedman sat down with 

to talk about FORCE and what patients should know about genetic testing and hereditary cancer risk.

: Why is it important for people to know more about genetic testing, especially in those families with a history of cancer? 

 There are a lot of reasons why it’s important to know this information, and one of the things that’s been exciting that’s coming out of ASCO but also other conferences over the years have been these new agents known as PARP inhibitors that are really targeted therapies and they were designed specifically for people with BRCA mutations although now they’re looking at how they work in other mutations as well. And so, right now these agents are approved for people with mutations and in some cases without mutations for ovarian cancer. In metastatic breast cancer, we’re really excited because there were some data presented here about treatment for pancreatic cancer in patients with inherited mutations. These studies are particularly exciting to FORCE because we were part of the efforts to help recruit patients and accrue for these clinical trials. Watching the data mature and be presented and watching that they’re very promising and hopeful is really exciting to us and it allows us to go back to the community and share that hopeful information with them.

The 23andMe test is a trending topic in this space, what should patients be aware of when it comes to these tests?

So, it’s important for patients to know about 23andMe. There’s a lot of media around it and we watch the media and respond to it for one of our programs known as XRAYS, but, what’s important for patients to know is that although the (Food and Drug Administration [FDA]) did clear 23andMe to return results to patients for these mutations, this is a very limited test. Out of the 5,000-plus mutations that are in BRCA1 and BRCA2 alone, this test only finds the three mutations found in people of Ashkenazi Jewish or Eastern European Jewish descent. So, it’s not a complete test.

The other important thing for people to know is that the FDA cleared 23andMe to return these results to patients but then they did say that patients should not rely on these test results to make medical decisions — they recommend a confirmatory test. One of the things we really worry about is the possibility that somebody might test negative for BRCA1 and BRCA2 according to 23andMe test, and as I said, there are thousands of other mutations, so they may think they’re clear and they don’t have a mutation when indeed there actually may be a mutation that they’re carrying. So, we strongly recommend that people speak to health care providers that are trained in cancer genetics before and after undergoing genetic testing.

How can these patients become better informed on genetic testing and advocate for themselves?

There are a few ways patients can become better informed and advocate for themselves with regard to genetics. One is that, certainly, if they need information, they can come to FORCE. We have many programs; we have a lot of information. We help them find the professionals who are trained in genetics and provide general information about what the next steps may be. But really, for someone who’s considering genetic testing we recommend genetic counseling. So, seeing a health care professional who has advanced training in genetics. They can talk to them about benefits and limitations of genetic testing, the laws that protect people from things like genetic discrimination, they can make sure individuals have the insurance coverage and if not they can give them information about programs that can help them pay for it, may pay out of pocket because you know because the cost of genetic testing has gone down a lot and also give them information that will empower their family members because one of the things that make these tests really important and different from other cancer tests is that they are shared by relatives. Inherited mutations can be passed down from one generation to the next generation. 

A breast cancer survivor and hereditary cancer expert discussed how patients can find accurate information about genetic mutations.

Sara Karlovitch

Two-Drug Combo Shows Modest Benefit in Biliary Tract Cancer

Lifting the Burden: How the Raymond Foundation Helps to Support Caregivers

What Patients Should Know About Genetic Testing and Hereditary Cancer Risk

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