MétaCan
Menu
Back to cohort
Record W4403537557 · doi:10.1016/j.esmoop.2024.103901

163TiP Single-institution, single-arm, open-label phase II basket study of mutation and/or elevated hedgehog (Hh) expression-directed smoothened inhibitor sonidegib in patients with advanced solid malignancies

2024· article· en· W4403537557 on OpenAlexfundno aff
M. De Silva, Krupesh Patel, Hao‐Wen Sim, Helen Wheeler, Michael Back, A. Guminski

Bibliographic record

VenueESMO Open · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHedgehog Signaling Pathway Studies
Canadian institutionsnot available
FundersCanadian Glycomics NetworkMinistry of Education, Culture, Sports, Science and Technology
KeywordsSmoothenedHedgehogHedgehog signaling pathwayMedicineMutationCancer researchInternal medicineOncologyBiologyGeneticsGene

Abstract

fetched live from OpenAlex

as partial response (PR) + complete response (CR), and disease control rate (DCR), defined as CR + PR + stable disease (SD).Results: 525 patients were treated on 98 EPCCTs.All patients received at least one dose of treatment with median of 4 cycles.93% of patients were off trial at data collection, 73.1% due to progression, 11% from toxicity.470 patients were evaluable for response.The ORR was 14.3% and DCR was 63.9%.Of the 238 patients with SD, 48.7% had duration of >6 months.The DCR in monotherapy (66.2%) and combination (62.8%) trials was similar.The difference in response rates due to sex (p 0.016), presence of liver metastasis (p¼0.0001),Royal Marsden Hospital prognostic score (p¼0.0001),Gustave Roussy Immune Score (p¼0.0001), and LDH (p¼0.0001) were all statistically significant.The median progression free survival was 4 months (SE 0.2, 95% CI 3.4-4.5)and median overall survival 10 months (SE 0.63, 95% CI 8.7-11.2).Patients with SD at 10 weeks have a 12-month survival probability of 0.53 (0.47-0.61) versus 0.12 (0.07-0.19) for PD.Table: 161P Category N % Age Median 60 years (18-83) Sex Female 256 48.8 Male 269 51.2 Ethnicity White 444 84.6 Asian 11 2.1 Black 4 0.8 Other 2 0.4 Unknown 64 12.2 Disease type Lung 131 25.0 Lower GI 86 16.4 Urological 63 12.0 Gynaecological 47 9.0 Breast 46 8.8 Other 152 28.9 Number of metastases 0 7 1.3 1 137 26.1 2 174 33.1 3+ 207 39.4 Liver metastases No 323 61.5 Yes 202 38.5 ECOG 0 160 30.5 1 359 68.4 2 6 1.1 Number of prior treatment lines 0 40 7.6 1 144 27.4 2 134 25.5 3+ 207 39.4 Trial treatment Monotherapy 353 67.2 Combination 172 32.8 Type of trial drug Chemotherapy 62 11.8 Drug conjugate 64 12.2 Immunotherapy 92 17.5 Targeted 229 43.6 Targeted + chemotherapy 24 4.6 Targeted + immunotherapy 38 7.2 Other 16 3.0Conclusions: EPCCTs are a valid treatment approach for patients with advanced cancer with two thirds of patients having DCR.Factors including LDH, presence of liver metastasis and sex contribute to the differences in response rates seen.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0060.001

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.

Opus teacher head0.034
GPT teacher head0.318
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueESMO OpenSame topicHedgehog Signaling Pathway StudiesFrench-language works237,207