Safety and antitumor activity of pembrolizumab in patients with advanced microsatellite instability–high (MSI-H) colorectal cancer: KEYNOTE-164
Bibliographic record
Abstract
Introduction: Approval of pembrolizumab as treatment for adult and pediatric patients with unresectable or metastatic previously treated MSI-H or mismatch repair–deficient cancer, regardless of tumor type or site, was partly based on data from cohort A of the phase 2 KEYNOTE-164 (NCT02460198) study of patients with MSI-H colorectal cancer (CRC) after ≥2 prior lines of standard therapy. Data are presented herein from cohort B of KEYNOTE-164, which was conducted to evaluate pembrolizumab in patients with metastatic MSI-H CRC previously treated with ≥1 line of therapy. Methods: Cohort B of the KEYNOTE-164 study enrolled patients with metastatic CRC who had locally confirmed MSI-H status per immunohistochemistry or polymerase chain reaction and had received ≥1 prior line of therapy (irinotecan, oxaliplatin, fluoropyrimidine, or anti-vascular endothelial growth factor/endothelial growth factor receptor). Patients received pembrolizumab 200 mg every 3 weeks (Q3W) for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed per RECIST v1.1 by independent review Q9W. End points included objective response rate (ORR) (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary). Results: Sixty-three patients were enrolled; median age was 59 years (range: 23-83); 52% were male. Most patients (94%) had ≥1 prior therapy for advanced disease; median number of prior therapies was 2. As of September 12, 2017, median follow-up was 12.6 months (range: 0.1-15.4). ORR was 32% (95% CI, 21-45), with 2 complete responses and 18 partial responses. Median DOR was not reached (NR); 95% of responses were ongoing; and DOR for 75% of responders was ≥6 months. Median PFS was 4.1 months (95% CI, 2.1-NR) and median OS was NR. The 12-month PFS rate was 41% and the 12-month OS rate was 76%. Forty (64%) patients experienced treatment-related adverse events (AEs) of any grade, most commonly (≥10%) fatigue (18%), hypothyroidism (16%), and hyperthyroidism (11%). Seven (11%) patients had grade ≥3 treatment-related AEs of anemia, thrombocytopenia, diarrhea, pneumatosis intestinalis, pneumonitis, syncope, arthritis, and vasculitis (n = 1 each). There were no treatment-related deaths. Twenty (32%) patients had immune-mediated AEs of any grade. Two (3%) patients had grade ≥3 immune-mediated AEs of pneumonitis and colitis (n = 1 each). Conclusion: Pembrolizumab demonstrated durable antitumor activity with a safety profile that was manageable in cohort B of KEYNOTE-164, which was conducted to evaluate patients with MSI-H CRC whose disease progressed after ≥1 line of prior therapy.
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 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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".