Initial analyses of a phase I/II trial of durvalumab (D) plus tremelimumab (T) and stereotactic body radiotherapy (SBRT) for oligometastatic head and neck carcinoma.
Bibliographic record
Abstract
6531 Background: PD-1/PD-L1 +/- CTLA-4 blockade in head-and-neck carcinoma (HNSCC) has shown signs of clinical activity. SBRT aims to reduce tumor burden and perhaps be immune-stimulatory. This analysis seeks to assess the safety and efficacy signal of the triple treatment combination (TTC) consisting of SBRT sandwiched between cycles of D (αPD-L1) and T (αCTLA-4) in oligometastatic (2-10) HNSCC. Methods: This is a single arm multi-institutional phase I/II trial (NCT03283605). D (1500 mg) and T (75 mg) were given for 4 monthly cycles, followed by monthly D. SBRT to 2-5 lesions was administered during cycle 2. The median prescribed and maximum SBRT doses were 40 Gy (range:18-50) and 49 Gy (range:28-61), respectively, given in 3-5 fractions. Global health status was derived from EORTC QLQ C30 questionnaires. Results: At data cut-off (Dec 31, 2019), 20 patients were recruited, of which 16 had a study treatment and were analyzed. Table describes the patient characteristics. There were 1 CTCAE V5.0 Grade 2 and 1 Grade 3 (both GI) serious adverse event (SAE) attributable to D and T. Two patients had unrelated SAEs (1 Grade 3-hypercalcemia and 1 Grade 5-GI). The Grade 5 SAE was a gastric hemorrhage that occurred the night of the first D + T infusion. There was no Grade 3+ AE secondary to SBRT. Thus, SBRT did not add to the 2/16 patients who had D + T related SAEs. Global health status scores did not differ statistically between baseline (75) and cycle 3 (73). Of the 14 patients that received SBRT, 7 patients had RECIST target lesions untreated by SBRT. The best responses for these 7 patients were: 1 CR, 3 PR, and 3 SD. When SBRT treated lesions are included and analyzed per RECIST (n = 14), there were 9 PR, 3 SD and 2 PD. The estimated median progression free survival was 7.2 months. Conclusions: The first 16 evaluable patients demonstrated tolerable profiles to the TTC (D + T + SBRT) for the treatment of oligometastatic (≤10 lesions) HNSCC. Best response rates were encouraging and could be due to the addition of SBRT during immunotherapy that served to either stimulate the immune system or annihilate slow responding or immunotherapy resistant lesions. Smaller overall tumor burden and 7/16 patients being treated in first line could also have contributed to better results. Clinical trial information: NCT03283605 . [Table: see text]
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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 | 0.004 | 0.002 |
| 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 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".