IND.210: A randomized phase 2 trial of FOLFOX6/bevacizumab with or without reovirus (Reo) in patients (pts) with metastatic colorectal cancer (mCRC).
Bibliographic record
Abstract
3546 Background: Reo, a serotype 3 reovirus, may preferentially infect and destroy cells with RAS activation. This trial evaluated the progression-free survival (PFS) of untreated mCRC pts treated with FOLFOX6/bevacizumab (q2 weekly) alone or with Reo (3x1010TCID50 on day 1-5 [cycles 1, 2, 4, 6, 8 then alternate cycles]). Methods: The trial had 80% power to detect improvement in PFS from 8.5 to 15.5 mo [Hazard ratio (HR) 0.55, α = 0.1]. Primary analysis adjusted for stratification factors (prior adjuvant chemotherapy, KRAS status) with sensitivity analyses (SA) adjusted for additional prespecified factors (gender, age, baseline LDH and Alk Phos). Secondary endpoints included overall response rate (RR), quality of life (EORTC QLQ C30), overall survival (OS). Results: Following safety run-in of 6 pts, 103 pts were randomized to FOLFOX6/bevacizumab with (n = 51) or without (n = 52) Reo. Pt characteristics: median age 60 (range 31-79), male (61.2%), ECOG 0: 45.6%, 1: 50.5% and 2: 3.9%. At median follow-up 13 months, PFS was significantly shorter in the Reo arm [median 7.3 vs 9.1 mo, HR 1.59 (95% CI 1.00 - 2.53) p = 0.046; SA HR 1.65, p = 0.04]. RR was higher in Reo treated pts [52.9 vs 34.6%, OR 2.09 (95% CI 0.96-4.55), p = 0.06; SA p = 0.03], but with a shorter median duration of response (5.1 versus 8.5 mo, p = 0.028). In subgroup analysis female pts had higher RR and longer OS than male pts but test for interaction was significant only for RR. There was no significant difference in hepatectomy rate (Reo 7.8% vs 3.8%), median OS (p = 0.48), or relative dose intensity of FOLFOX6 or bevacizumab. Reo pts had worse QLQ C30 physical functioning (mean change score from baseline -3.9 vs. 1.94; p = 0.008). The most common adverse events (AEs) of any grade attributed to Reo were fatigue (51%), fever (49%), chills (44%), and anorexia (33%). With respect to grade 3+ AEs, pts on Reo experienced more hypertension (26.3 vs 3.8%, p = 0.001), more proteinuria (22.8 vs 1.9%, p = 0.001); and less abdominal pain (3.5 vs 17.3, p = 0.02) than the control arm. Conclusions: While the addition of Reo to FOLFOX6/bevacizumab increased RR; PFS, toxicity and QoL were significantly worse. Further follow-up of maturing OS data is planned. Clinical trial information: NCT01622543.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".