ESMO 2022 Research Update: A Patient Research Advocate Viewpoint

October 19, 2022 • By Fight CRC

Clinical Trial Conversations
hero symbol

For this month’s Clinical Trials Conversations blog, we interviewed Annie Delores, a patient research advocate who, after joining Dr. Tom Marsilje’s CRC Trials Groups in 2016, has pursued an interest in looking at clinical trial options. In January 2020, she joined the Fight CRC Research Advocate and Training Program (RATS).

There are five main oncology conferences for presentation of research specially relevant for gastrointestinal cancers: ASCO Annual meeting, ASCO-GI, AACR, ESMO World GI Symposium, and the ESMO Annual meeting. This past September, the Annual ESMO (European Society of Medical Oncologists) Congress met in Paris. We interviewed Annie, one of Fight CRC RATS volunteers, to help unpack the most important findings for our community recently presented at ESMO.

ESMO 2022 Research News

Earlier this year, at ASCO, we heard about remarkable results from immunotherapy (anti-PD1) for some rectal cancer patients – those with stage II and III, deficient mismatch repair system/microsatellite instability (dMMR/MSI-H) rectal cancer. And the good news continued at ESMO, for the MSI colon cancer subset of patients, now with a combination of immunotherapies. Can you tell us more about it?

The NICHE-2 study received a standing ovation at ESMO 2022. Dr. Myriam Chalabi, from the Netherlands, presented data for response to one dose of immunotherapy for stage III colon cancer patients with MSI. The trial showed 95% major pathologic responses (67% were Pathological Complete Responses, “pCR’).

A lesser known result: The study also showed an increased response for Lynch Syndrome patients (78% pCR vs. 58% pCR). Dr. Chalabi talks about the NICHE-2 study in this ESMO22 interview.

Fifteen percent of all colorectal cancers are part of the MSI subtype (about 10% of stage III colon cancer patients). Right now, for immunotherapy options, there is the ATOMIC trial (immunotherapy after chemo) and the StandUp2Cancer trial (immunotherapy after chemo if there is a positive circulating tumor DNA (ctDNA) result). Chemotherapy with oxaliplatin can bring on neuropathy side effects (which can affect one’s ability to work in many careers (neuropathy in hands) or can increase risk of falling for elderly patients (with neuropathy in their feet). For stage III colon cancer patients, surgery side effects, while manageable, are not minimal (bowel issues). Having a trial where surgery or chemo may be avoided would be an exciting option for patients and worthy of discussion with an expert oncologist.

What about some news for all patients (with colon or rectal cancer), regardless of mutations or microsatellite status? We’re always looking to hear about phase III trials that may result in the approval of new therapies, leading to a change of practice.

Options for stage IV patients in later lines after progression on chemo are limited. So the phase III FRESCO-2 trial looking at Fruquintinib (approved in China in 2018) was to demonstrate safety and efficacy. FDA approval is possible in the coming months (it was Fast Tracked in June 2020). The trial demonstrated benefit to patients, as well as tolerable side effects of the treatment. This interview with Dr. Arvind Dasari explains the trial results (along with some of his ESMO22 slides).

I’ve been watching this trial for awhile. There have been 33 trials in China, four in the U.S. (one of which was also recruiting in Europe), and one in Australia for fruquintinib. There are two trials open in the U.S. (one of which is for colorectal cancer patients and is combining immunotherapy: NCT04577963). There are 23 trials open in China as researchers are combining fruquintinib with other chemotherapies, biologics, or immunotherapies, as well as moving the use of fruquintinib into earlier lines of therapy.

Patients will want to consider possible benefits, as well as side effects especially as compared to options such as regorafenib (Stivarga®) or TAS-102 (also known as trifluridine–tipiracil) (Lonsurf®). Although there are patients who benefit from Stivarga and Lonsurf, the side effects can be problematic.

Post chemotherapy, oncologists have to look at many factors in prescribing a treatment for their patients (risk factors, comorbidities, etc.), since hypertension was one of the grade 3 side effects, that may be relevant to their recommendation for fruquintinib. The trial was a comparison against a placebo, so oncologists will be looking at historical data for Lonsurf® and Stivarga® for progression free survival. But the reported ESMO side effects data may be very important for their recommendations.

Have there been any findings pertinent for those with colorectal cancer with particular mutations? Any news from the targeted therapies front?

But in colorectal cancer, a monotherapy (a targeted drug given on its own) did not give enough benefit for such an approval. Researchers working in another colorectal cancer mutation, BRAF V600e, learned in the BEACON study that using a dual blockade of a targeted treatment with an EGFR inhibitor worked for better response for BRAF V600e patients (which led to the BEACON doublet becoming FDA-approved standard of treatment).

Similarly, for KRAS G12C colorectal cancer treatment, researchers have added in an EGFR inhibitor: cetuximab (with adagrasib, in the KRYSTAL-1 trial) or panitumumab (with sotorasib, in the CodeBreak-101 study). Both clinical trials are now showing improvement in response rate, progression free survival, and overall survival for patients in the KRYSTAL-1 and the CODEBREAK-101 trials (compared to researchers' prior trials for these two drugs).

Although KRAS G12C makes up about 2% of colorectal cancers, this dual MAPK pathway inhibition may become a strategy in other targeted KRAS trials. These trials are now in early monotherapy phase trials seeking to establish safety and efficacy. Other MAPK pathway interventions being considered: SHP2 inhibitor, SOS-1 inhibitor, MEK inhibitor, and ERK inhibitors.

Because of the discovery that KRAS G12C was “druggable,” there has been a lot of research and investment in a variety of KRAS targeted approaches. The trials are offered in the second-line metastatic setting, but there are also KRAS trials for those with minimal residual disease (NED on scans, positive ctDNA result). 

This area of KRAS research is moving fast, and for the 40% of stage IV patients with a KRAS mutation, checking in on KRAS research at all the important conferences is well-recommended.

MOUNTAINEER-2 trial results continues its trifecta of summer oncology conference presentations (ASCO, World GI, ESMO). This non-chemotherapy trial is for HER2 positive (HER2+) colorectal cancer patients. Response rates are quite good, and treatment side effects manageable.

Although HER2+ is not common (about 3%) of all colorectal cancer patients, about one out of seven rectal cancer patients have this targetable mutation. It’s also more common with left-sided colon cancer patients, so testing for this mutation is well-advised!

In the past few years, KRAS G12C targeted treatments have been enrolling patients across tumor types. One-treatment sotorasib (Lumakras®) has an FDA-accelerated approval for non-small cell lung cancer.

Dr. Strickler is rather a quiet hero of scientific research. He noticed that HER2+ patients responded differently to a treatment and approached a pharma company Seattle Genetics (not to be confused with SEAGEN, which is a different company) with an investigator-initiated study. Because of early positive results of the first MOUNTAINEER trial, the NCCN Guidelines now include the suggestion that oncologists consider trials with trastuzumab (Herceptin®) in combination with other medications as a second-line option. At this annual ESMO Congress, Dr. Strickler reported the results from the phase II MOUNTAINEER-2 study.

Interview with Dr. Strickler (from ESMO World GI, July 2022) on how tucatinib plus trastuzumab yields clinically meaningful antitumor activity in HER2+ metastatic colorectal cancer.

The next trial, the MOUNTAINEER-3 study, is now at 25 locations, enrolling 400 patients, and is moving this treatment into a first-line setting. The trial will test if response rates may be even higher in an earlier line of treatment and if there is a longer durable response to this well-tolerated treatment. The trial is also open to stage III HER2+ patients who progress to stage IV (if chemo was completed more than six months prior to enrollment). In this interview from July, Dr. Strickler talks about this phase III trial now recruiting.

This was a great overview of news from ESMO 2022 that affects, impacts, and matters to us. Thank you, Annie, for helping us to understand the progress and where the research is headed!

Stay Tuned for More Colorectal Cancer Clinical Trials Conversations!

Once a month, Maia and Manju will spend time unpacking important research trials, tips, and advice for our community. Be sure to subscribe to sign up with Fight CRC and join COLONTOWN’s online community to continue receiving the most relevant updates in the colorectal cancer world!

You can also follow Maia (@sassycell) and Manju (@manjuggm) to stay updated on research and trials and visit ClinicalTrials.gov for more information on trials.

Be Sure to Check Out These Fight CRC Resources

Clinical Trial Finder

More Clinical Trial Conversations

Clinical trials are critical to finding a cure for colorectal cancer. As an advocacy organization dedicated to supporting and empowering a community of patients, caregivers and families, Fight CRC has partnered with COLONTOWN to deliver a monthly blog series highlighting everything patients need to know about clinical trials and the best treatment options available. 

In this series, we hope to cover promising trials that are enrolling, lessons learned from past research, logistics and resources to joining a clinical trial, and provide relevant and timely updates for our colon and rectal cancer community.