Immune related adverse events (irAE) with platinum chemotherapy (CT) with durvalumab (D) ± tremelimumab (T): CCTG IND226.
Bibliographic record
Abstract
3058 Background: CT is immunomodulatory and requires corticosteroids (CS) premedication. We hypothesized that the incidence of irAE may be lower when D ± T is given with CT or CS. Methods: Patients (pts) receive CT (pemetrexed, nabpaclitaxel, etoposide or gemcitabine + cisplatin or carboplatin; usual 4-6 cycles) with D ± T, followed by D ± T alone (1 year total); pts with ≥ g2 (selected) or ≥ g3 irAE discontinued D ± T. Cycles were coded as CT + D ± T or D ± T; pts could contribute to both. CS: high (dexamethasone > 10mg/day for 5 days) or low CS. irAE were D ± T related gastrointestinal (GI), skin, endocrine, neurologic, hypersensitivity, pneumonitis (PN) or other immune (nephritis (GN), pancreatitis, hepatitis). Biochemistry (BIO; all causality): creatinine, transaminases/bilirubin (LFTS) and amylase/lipase was summarised. Results: In this ongoing study, 118 pts received 723 cycles. Pts had good performance status (PS 0-1), 78 had thoracic malignancies and 84 no prior CT. 44 pts continue on D ± T alone; 32 pts continue on CT + D ± T while 76 pts discontinued D ± T primarily due to disease progression; 15 discontinued for ≥ g2 irAE [PN (3), hepatitis (1), GN (2), adrenal (1), myocarditis (1), GI (3), thrombocytopenia (1), hyperthyroidism (1), encephalitis (1), pt decision (1)]. 67 pts had high CS cycles while 78 pts had low. 50% pts had irAE and 10% had ≥ g3 irAE, most commonly skin and GI. GI (15 vs 11%), skin (26 vs 20%) and PN (3 vs 0%) were reported in more pts during CT + D ± T cycles (non significant (NS)) ; hypothyroidism was more common with D ± T alone (18 vs 10%; p = NS). IrAE rates and severity were similar between high (67 pts) or low CS (78 pts) except for GI (19 vs 10%; p = NS). BIO were more common during CT + D ± T (74% of pts vs 48% p = 0.003); rates in high CS were similar to low CS. LFTs (ALT/AST - 41% vs 16%; 38% vs 9%; p = 0.005) and amylase/lipase (18 vs 9%; 19 vs 14%; p = NS) were more common in pts with CT + D ± T cycles vs pts with D ± T alone cycles. Conclusions: There is no evidence that CT or CS abrogates irAE in this exploratory analysis. GI, skin, pneumonitis, LFTS and amylase/lipase were more common during CT + D ± T suggesting additive/multifactorial causes; hypothyroidism is more common in D ± T cycles, which may reflect time on treatment. Clinical trial information: NCT02537418.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| 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".