Safety of radiotherapy with concurrent and adjuvant MEDI4736 (durvalumab) in patients with locoregionally advanced head and neck cancer with a contraindication to cisplatin: NRG-HN004.
Bibliographic record
Abstract
6065 Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell carcinoma (HNSCC). A phase II/III trial with lead-in component was designed to evaluate the safety and efficacy of concurrent and adjuvant MEDI4736 with radiation therapy (RT) for HNSCC patients with a contraindication to cisplatin. Safety data for 10 patients on the lead-in study are reported. Methods: Eligible patients had previously untreated locoregionally advanced unresected SCC of the larynx, hypopharynx, oropharynx (OPX), oral cavity, or unknown head/neck primary (AJCC 7th stage III-IVB). Contraindications to cisplatin included renal or hearing impairment, age ≥ 70 with moderate or severe comorbidity/vulnerability to cisplatin, or age< 70 with severe comorbidity/vulnerability, based on 6 validated indexes. Intravenous MEDI4736 1500 mg was delivered at weeks -2, 2, 6, 10, 14, 18, and 22 with RT (70 Gy in 35 daily fractions weeks 1-7). The primary endpoint was dose-limiting toxicity (DLT), defined as a high-grade adverse event (AE; NCI CTCAE version 4.0) definitely/probably related to MEDI4736 up to 4 weeks following completion of RT; 0-2 DLTs in 8 evaluable patients was considered acceptable. Results: Characteristics of the 10 enrolled patients were: 30% age ≥ 70, 90% male, 100% Caucasian, 40% ECOG performance status 0, 60% modified Charlson Comorbidity Index ≥ 1, 60% >10 pack-years, 20% larynx, 60% p16+ OPX, 50% T3-4 and 80% N2-3 disease. All 10 patients had ≥ 2 contraindications to cisplatin. All 10 patients completed RT and were evaluable. 8 of 10 patients received all 7 doses of MEDI4736 and 1 patient is still on MEDI4736 after 6 doses. 1 patient received 2 doses then discontinued due to AE (diarrhea possibly related to MEDI4736). No DLTs were observed. No grade 4-5 AEs were observed. Grade ≥ 3 AEs possibly related to MEDI4736 were: diarrhea (n=1), nausea (1), and vomiting (1). No grade ≥ 3 AEs were rated as definitely or probably related to MEDI4736. Conclusions: MEDI4736 is safe and feasible to administer concurrently with RT for patients with HNSCC with a contraindication to cisplatin. Clinical trial information: NCT03258554.
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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) | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".