Expert Details 'Striking' Data When Using ctDNA to Predict Early Response in CRC

ctDNA, as assessed by the G360 response algorithm, appeared to be predictive of early treatment response in patients with advanced colorectal (CRC) cancer and could provide valuable early insight, according to Pahstoon Kasi, MD, MS.

These findings read out at the 2023 Gastrointestinal Cancers Symposium. During the meeting, CancerNetwork^® spoke with lead author Kasi, a medical oncologist from Weill Cornell Medicine, regarding the data and their significance in the CRC space.

Investigators reported that the overall survival for patients who responded to treatment with chemotherapy was not reached (NR; 95% CI, 26.3-NR; CPH HR, 0.17; 95% CI, 0.08-0.36; P <.005) and 11.8 months (95% CI, 8.7-14.6) for patients who did not respond (HR, 5.92; 95% CI, 2.78-12.63; P <.005).

The median TTNT for those who responded to treatment with chemotherapy was 10.3 months (95% CI, 7.3-NR; HR, 0.51; 95% CI, 0.28-0.92; P = 0.26) and 5.8 months for non-responders (95% CI, 4.0-7.4; HR, 1.97; 1.08-3.58; P = .026).

Transcript:

In our cohort of individuals—diving down deeper into what we found—we chose a 50% decrease as an arbitrary cut-off. In our analysis, we did show that across a range of cohorts, whether it’s 10%, 20%, 30%, or all the way up to 80%, that pattern of benefit in terms of progression-free survival or overall survival was something that was seen across the board.

It’s more so the concept of decline in ctDNA that is something to keep in mind. What was striking as we talked about patients with metastatic colorectal cancer was if you look at some of the recent trials, randomized data, or outcomes published through some of these national databases, we’re talking about median survival of upwards of 3 years or 4 years. Obviously, some patients derive more benefits and some derive less benefits from therapies.

In the non-responder [group], somebody who didn't respond based on the definition we had [outlined for the trial], our median overall survival was less than a year, 11.8 months to be specific, whereas the median survival in the responder [group] wasn’t even reached. That was similar across the board where patients were on other regimens where a biologic was added, that was around 17 months [for non-responders], but again, not reached [for responders] in the overall cohort.

Very quickly and very early on, within a month, we were expecting some differences. These were even more striking than anticipated in terms of how powerful these tools can [beyond determining time to] next treatment. Somebody could argue [response will be revealed in the] next scan in 2 months or 3 months but sometimes having that early insight into who is responding and who is not responding is something that is of value. The fact that it could also equate to overall survival is very powerful and could a provide quick readout as early as a few weeks with no therapy.

Reference

Kasi PM, Weipert C, Nguyen T, et al. Use of circulating tumor DNA (ctDNA) for early assessment of treatment response in patients with advanced colorectal cancer (aCRC): A real-world (RW) analysis. J Clin Oncol. 2023;41(suppl 4):246. doi:10.1200/JCO.2023.41.3_suppl.246