Effects of liver metastases on efficacy of immune checkpoint blockade in treatment refractory, metastatic colorectal cancer (CRC): CCTG CO.26.
Bibliographic record
Abstract
3600 Background: Immune checkpoint blockade has limited activity in microsatellite-stable (MSS) or mis-match repair proficient (pMMR) CRC. Recent findings suggest that immunotherapy efficacy may be modulated by the presence of liver metastases. We conducted a retrospective analysis of the Canadian Cancer Trials Group (CCTG) CO.26 study to investigate the relationship between the presence of liver metastases and activity of immune checkpoint blockade. Methods: The CCTG CO.26 study was a randomized phase II study (NCT02870920). Pts with treatment refractory CRC were randomized to durvalumab, tremelimumab and best supportive care (BSC) or BSC alone in a 2:1 fashion. Treatment consisted of durvalumab (1500 mg) q 28 days and tremelimumab (75 mg) q 28 days for the first 4 cycles. The primary endpoint was overall survival (OS) and a two-sided p-value <0.10 was considered significant. Results: Between 08/20106-06/2017, 180 pts were enrolled and 179 treated as randomized. Pt baseline characteristics were balanced between groups. With a median follow-up of 15.2 months, the median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for BSC (p = 0.07; Hazard ratio (HR): 0.72, 90% confidence interval (CI): 0.54 – 0.97). Progression free survival (PFS) was 1.8 months and 1.9 months respectively (HR 1.01, 90% CI: 0.76 – 1.34). Disease control rate (DCR) was 22.6% for durvalumab and tremelimumab and 6.6% for BSC (p = 0.006). At study entry, liver metastases were absent in 29.4% pts. Pts without liver metastases had improved OS compared to those with liver metastases, irrespective of treatments. PFS was significantly longer in those without liver metastases on durvalumab and tremelimumab (HR: 0.55, 90% CI: 0.31 – 0.97, p = 0.08, interaction p = 0.02). DCR was 49% in patients without liver metastases with durvalumab and tremelimumab, compared to 10% in those with liver metastases (Odds Ratio: 0.12, 90% CI: 0.05 – 0.26). Conclusions: Pts without liver metastases had improved OS and PFS, and higher DCR. Absence of liver metastases may be an indicator for improved efficacy of immune checkpoint blockade and should be investigated in future studies. [Table: see text]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".