News from Annual ASCO Meeting about Clinical Trial Results for Colorectal Cancer

• 

Clinical Trial Conversations
hero symbol

This June, as every year, researchers from across the globe, clinicians, pharmaceutical companies, and patient advocates come together – in person for the first time since 2019 – to attend the American Society of Clinical Oncology’s (ASCO) annual conference, the largest oncology conference in North America.

We know our community has questions about the latest exciting colorectal cancer research updates, and we wanted to talk about them here.

This month’s Clinical Trial Conversations focuses on Maia and Manju’s top abstracts from ASCO 2022 that are pertinent for the colon and rectal cancer community. 

Exciting colorectal cancer clinical trials

Please outline for us the news/abstracts from ASCO 2022 that caught your attention, and you think are important for the colorectal cancer community to be aware of. We would also love to hear the impact these findings could have on future care for those facing colorectal cancer.

  • The phase 3 PARADIGM trial results presented are treatment changing – in this case, for some patients who are receiving first-line chemotherapy for their metastatic colorectal cancer. The study showed that adding panitumumab (Vectibix®) to the usual chemotherapy (Folfox) works better (“significantly improved overall survival”) than adding bevacizumab (Avastin®) for patients with left-sided, RAS wild-type metastatic colorectal cancer (mCRC). Abstract: LB1 Trial: NCT02394795
  • From the phase 3 CAIRO5 trial, which investigates the best treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, results show that three chemotherapies (Folfoxiri) added to bevacizumab (Avastin®) work better than two chemotherapies (Folfox or Folfiri) added to bevacizumab, but at the expense of more toxicity.
    • For the “higher risk” colon cancer population (RAS or RAF mutates, or right sided),  Folfoxiri plus bevacizumab might be considered when possible, since it offers better progression-free survival (PFS) and response rates, and increases the chances of resection. Abstract: LBA3506 Trial: NCT02162563
  • Results from the phase 3 TRIPLETE trial shows that the “hit harder” approach is not always the best. In mCRC patients, RAS and BRAF wild-type, the EGFR inhibitor panitumumab (Vectibix) plus a stronger chemotherapy regimen (Folfoxiri) did not demonstrate a significant response benefit, compared to just Folfox plus panitumumab. In other words, there was no significant difference in PFS, early tumor shrinkage, etc., for those receiving a harsher chemotherapy combination. Abstract: LBA3505 Trial: NCT03231722

Circulating tumor DNA (ctDNA) tests

Several clinical trial results presented during ASCO 2022 show how liquid biopsy circulating tumor DNA (ctDNA) tests are becoming more relevant to treatment decisions in colorectal cancer: the Australian trial DYNAMIC, the MD Anderson anti-EGFR rechallenge, and the Japanese trials REMARRY and PURSUIT (Abstract 3518):

  • The Australian phase 2 randomized DYNAMIC study demonstrated how guided approaches considering ctDNA status reduced the number of patients who received adjuvant chemotherapy, without the risk of lowering recurrence-free survival rates for some patients with stage II colon cancer. “The low recurrence rate in ctDNA-positive patients who received chemotherapy suggests a survival benefit from adjuvant therapy. Patients who are ctDNA-negative are unlikely to benefit from chemotherapy,” concluded the study. Abstract: LBA100 Trial: ACTRN12615000381583
  • The MD Anderson anti-EGFR rechallenge aimed to evaluate how revisiting panitumumab would work, with the addition of a MEK inhibitor (trametinib) or on its own (in any case, without the addition of chemotherapy).
    • Trametinib did not improve efficacy, and of 22 patients that crossed over to add trametinib, none had a response. However, it is remarkable that the ctDNA test before starting the study was used to enroll patients in the different arms. The overall response rate (ORR) was 20% in those that did not have RAS mutation at time of initiation; PFS was 4.1 and overall survival (OS) was 11.2 months. On the other hand, the ORR was 0% in those that did have RAS mutation at time of initiation.
    • This shows the importance of using ctDNA tests to guide decisions about rechallenge, and potentially benefit a 20% of those patients without acquired resistance. Abstract: 3520 Trial: NCT03087071

Hope for MSS colorectal cancer

Finally, let’s consider a couple of trials that bring hope in the immunotherapy for microsatellite stable (MSS) colorectal cancer front:

  • The phase 2 NIVACOR trial, ongoing at several Italian locations, investigates how well the addition of immunotherapy works in the first line of therapy for some metastatic colorectal cancer patients with a high unmet need for new treatment options: Those who have RAS and BRAF mutated cancers.
    • The trial enrolled both MSS and microsatellite instability-high (MSI-H) colorectal patients. The immunotherapy nivolumab (Opdivo®, a PD-1 checkpoint inhibitor) was added to the standard of care combination Folfoxiri plus bevacizumab. So far, the primary endpoint ORR was met at 76.7% (complete response in 9.6% of total patients, partial response in 67.1%). Promising activity was observed also in the MSS subgroup, so this phase 2 trial, not randomized, will likely lead to the conduction of a phase 3 randomized-controlled study. Abstract: 3509 Trial: NCT04072198
  • Another study investigating the addition of immunotherapy for resectable/early-stage colon cancer shows some preliminary good results, even for MMRp (mismatch repair proficient, which results in MSS), usually unresponsive to immunotherapy as monotherapy.
    • NICHE, a clinical trial that is taking place in the Netherlands, researches how well short-term immunotherapy works when given before surgery to resect stage I, stage II and stage III colon tumors. The patients with MMRd (mismatch repair deficient, which usually means MSI-H) colorectal cancer received nivolumab and ipilimumab (two different immunotherapies, checkpoint inhibitors). Half the MMRp patients received that same combination, while the other MMRp patients also received celecoxib (a COX2-inhibitor, an anti-inflammatory drug) along with the immunotherapies combination.
    • While the pathologic response observed in 100% of the MMRd patients may be not surprising (see the response to dostarlimab covered in the first abstract in this blog), the response in MMRp is promising: in this MSS group, pathologic response was observed in nine of 30 patients (30%), consisting of seven major pathologic responses (including three pathologic complete responses (pCR) and two partial responses (PR).
    • Four out of nine MMRp patients who had a major pathologic response had received celecoxib. The 30% response rate in this small phase 2 trial was among the highest response rates reported in MMRp colorectal cancer. Abstract: 3511 Trial: NCT03026140

More Fight CRC ASCO 2022 Resources

Science can be a lot to unpack and understand – that’s why we provide numerous resources to help explain research in a way patients can understand. Check out Fight CRC’s recent webinar with Dr. Timothy Cannon, from Inova Health, in which he talks about the colorectal cancer research updates from the 2022 ASCO Annual Meeting.  Be sure to also view the recent IG Live with Danielle Ripley-Burgess, Fight CRC’s chief storyteller, and Dr. Cathy Eng from Vanderbilt-Ingram Cancer Center,

Maia and Manju

If you haven’t met Maia or Manju yet – learn more about them now!

Stay Tuned for More!

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 CRC 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.

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. 

Leave a Reply

Your email address will not be published.