KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC.
Bibliographic record
Abstract
9013 Background: Pembro + chemo significantly improved OS and PFS over chemo alone and had manageable safety as 1L therapy for metastatic nonsquamous NSCLC in the KEYNOTE-189 study (NCT02578680). The benefit was observed irrespective of PD-L1 TPS. We present updated OS based on longer follow-up and, for the first time, PFS2. Methods: Eligible pts were randomized 2:1 to pembro (n = 410) or placebo (n = 206) + pemetrexed and carboplatin or cisplatin for 4 cycles followed by pembro or placebo for up to 35 cycles + maintenance pemetrexed. Pts in the chemo arm could crossover to pembro alone upon PD. Poststudy anticancer therapy and outcomes were collected. PFS2 was defined as time from randomization to PD per investigator after start of 2L therapy or death, whichever occurred first. There was no multiplicity adjustment, and all P values are nominal. Data cutoff was 21 Sep 2018. Results: With 18.7-mo median follow-up, pembro + chemo continued to provide longer OS (HR 0.56 [95% CI 0.45-0.70], P < .00001; median 22.0 mo vs 10.7 mo) and PFS (HR 0.48 [95% CI 0.40-0.58], P < .00001). Benefit was seen in all PD-L1 TPS groups (Table). 2L+ therapy was received by 45% in the pembro + chemo arm and 59% (54% 2L+ immunotherapy) in the placebo + chemo arm. PFS2 was longer for 1L pembro + chemo (HR 0.49 [95% CI 0.40-0.59], P < .00001; median 17.0 mo vs 9.0 mo), with no difference by TPS (Table). Conclusions: 1L pembro + pemetrexed/platinum continued to show substantial OS benefit in metastatic nonsquamous NSCLC, regardless of PD-L1 TPS and despite 54% of pts in the placebo + chemo arm receiving subsequent immunotherapy. Median OS, PFS and PFS2 were approximately doubled with pembro + chemo. These data confirm that pembro should be given as part of 1L therapy to maximize outcomes in both PD-L1expressing and PD-L1non-expressing NSCLC. Clinical trial information: NCT02578680. [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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 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".