Abstract CT207: Association of gene expression profiles and clinical outcomes in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma treated with pembrolizumab in KEYNOTE-629
Bibliographic record
Abstract
Abstract Background: Pembrolizumab (pembro) monotherapy demonstrated clinically meaningful antitumor activity for both locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) in the phase 2 KEYNOTE-629 trial (NCT03284424). cSCC has high immunogenicity driven by a high tumor mutational burden and it is of interest to determine if the 18-gene T-cell inflamed gene expression profile (TcellinfGEP) and a set of other signatures relevant to the tumor microenvironment are associated with response to treatment. This retrospective analysis aimed to evaluate the association between GEP signatures and clinical outcomes in patients (pts) treated with pembro in KEYNOTE-629. Methods: Pts with histologically confirmed LA or R/M cSCC, measurable disease per RECIST v1.1, ECOG PS 0 or 1 received pembro 200 mg IV Q3W ≤35 cycles. Association between TcellinfGEP by RNAseq with clinical response (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) to pembro, and association between a set of additional consensus signatures with clinical response to pembro adjusted for TcellinfGEP were evaluated. Significance of GEP signatures was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included TcellinfGEP AUC or Harrell’s C-index in predicting response to pembro. Results: Of 159 pts, 143 (n = 52, LA cSCC; n = 91, R/M cSCC) had RNAseq samples available for analysis. Of 143 pts, 33.6 % had a TcellinfGEP <1st tertile and 66.4% had a TcellinfGEP ≥1st tertile. TcellinfGEP was significantly associated with improved ORR (P = 0.040) but not PFS (P = 0.087) or OS (P = 0.709). None of the 10 other consensus signatures were significantly associated with clinical outcomes after adjusting for TcellinfGEP and multiplicity (P > 0.05). AUC of TcellinfGEP was moderately predictive of ORR (0.61, 95% CI, 0.51-0.70). Harrell’s C-index of TcellinfGEP was moderately predictive of PFS (0.57, 95% CI 0.51-0.63), and duration of response (0.56, 95% CI 0.38-0.73), but not predictive of OS (0.50, 95% CI 0.42-0.57). Median PFS (95% CI) was 4.1 mo (1.4-9.8) for the TcellinfGEP <1st tertile subgroup and 8.5 mo (5.5-21.0) for TcellinfGEP ≥1st tertile subgroup. Median OS (95% CI) for the TcellinfGEP <1st tertile subgroup was 25.1 mo (11.4-NR) and 21.0 mo (15.8-29.8) for the TcellinfGEP ≥1st tertile subgroup. Conclusions: In this retrospective analysis of KEYNOTE-629, Tcellinf GEP was associated with tumor objective response to pembro, but was not clearly associated with longer survival in pts with LA or R/M cSCC treated with pembro. While definitive conclusions require more analyses, these findings provide additional support for TcellinfGEP as a predictive biomarker for cSCC. Citation Format: Åse Bratland, Jean-Jacques Grob, Eva Munoz Couselo, Laurent Mortier, Ralf Gutzmer, Osama Roshdy, Rene Mendoza Gonzalez, Jacob Schachter, Ana M. Arance Fernandez, Florent Grange, Nicolas Meyer, Abhishek J. Joshi, Salem Billan, Judong Shen, Razvan Cristescu, Michael Nebozhyn, Andrey Loboda, Jason Sparkowski, Burak Gumuscu, Jianda Yuan, Brett Hughes. Association of gene expression profiles and clinical outcomes in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma treated with pembrolizumab in KEYNOTE-629 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT207.
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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 | 0.000 |
| 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) | 0.001 | 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".