Hyperprogressive disease in advanced triple-negative breast cancer (aTNBC) treated with immunotherapy (IO).
Bibliographic record
Abstract
1086 Background: Hyperprogression of disease (HPD), a rapid acceleration of tumor growth rate (TGR) has been reported with IO in other tumor types. Here, we explore HPD in aTNBC. Methods: A retrospective chart review identified aTNBC patients who consented for IO clinical trials at Princess Margaret Cancer Centre between June 2013 and June 2018. Demographic data, medical history, details of trial enrolment and RECIST 1.1 response to study treatment were recorded. Patients with RECIST 1.1 measurable disease on CT scans or physical examination before trial entry, at trial baseline and at protocol-defined interval following IO start were evaluable for TGR as defined by Champiat et al. Clin Cancer Res 2017. HPD defined as a ≥2-fold increase in TGR between baseline and on-trial restaging assessment. Univariable logistic regression used to identify variables [age, co-morbidity index, prognostic index, performance status, distant disease free interval (dDFI), lactate dehydrogenase, no. of metastatic sites, visceral disease and no. of prior treatment lines] associated with HPD. Overall survival (OS) curves were estimated with the Kaplan-Meier method and compared by the log-rank test. Results: 99 patients with aTNBC consented for 15 IO clinical trials, 60% IO monotherapy, 22% chemotherapy+/-IO and 18% IO combinations. Median age 52 (range 25-78), median no. of lines of prior systemic therapy for advanced disease 1 (range 0-8). 15% had de-novo metastatic disease, 58% recurred after a dDFI of < 3 years and 25% after a dDFI of > 3 years. 61% had < 3 metastatic disease sites, and 71% had metastases involving the viscera. 66 received IO treatment, 40 patients (20 monotherapy, 7 IO combination, 13 chemotherapy+/-IO) were evaluable for TGR. Median TGR pre-IO was 74.3 (range -17 – 1680) and post-IO was 2.5 (-71.4 – 223). 4 patients (10%) met criteria for HPD. All 4 treated with monotherapy PD1 inhibitor and received at least 2 further lines of therapy post-trial; 1 patient treated with IO as first-line therapy, 3 in the second or later lines. There was no significant difference in the overall OS of patients with HPD and patients who did not meet definition for HPD HR 0.89, (95% CI: 0.26-3.01; p = 0.41). Univariable analysis did not identify factors associated with HPD. Conclusions: HPD was observed in 10% of aTNBC treated on IO clinical trials. HPD was not associated with worse survival outcomes or known prognostic factors in our analysis.
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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) | 0.000 | 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".