Long term outcomes of patients with advanced/unresectable melanoma treated with immune checkpoint inhibitors.
Bibliographic record
Abstract
e21518 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced/unresectable melanoma. There is a need for long term follow up of patients (pts) treated with ICIs in the real world to evaluate durability of response and facilitate follow-up care. Methods: Pts ≥ 18 years (y) old with advanced/unresectable melanoma who received ≥ 1 cycle of ICI at BC Cancer between 2012 and 2022 were identified using the BC Cancer Registry and pharmacy databases. Best overall response of complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) was obtained from CT and PET reports. Oligo-progression that was successfully treated with local therapy was not considered true progression. Results: In total 530 pts were identified. The median follow up for alive pts was 65 months (m) (range 1.4 – 150 m); the median age was 66 y (range 21 – 98). The majority were male (63%) and Caucasian (91%), with ECOG performance status 0 (38%) or 1 (48%). Primary tumour origin was cutaneous (n = 390, 74%), mucosal (n = 36, 7%), ocular (n = 47, 9%) or unknown (n = 57, 11%). BRAF V600 mutations (mut) were identified in 35% of pts (40% cutaneous/unknown). Pts either received PD-1 inhibitor alone (PD-1i) (n = 242, 46%), combination ipilimumab and nivolumab (ipi/nivo) (n = 136, 26%), ipilimumab alone (ipi) (n = 83, 16%) or sequential use of ipi and PD-1i (sequential) (n = 69, 13%). Overall survival (OS) was superior in cutaneous/unknown (5 y 34.5%) compared with mucosal (5 y 28%) and ocular (5 y 5%) primaries (p < 0.001). Excluding ocular cases for the ensuing analyses, by treatment group (ipi/nivo, PD-1i, ipi, sequential) the 5 y OS was 43%, 36%, 37% and 10%, respectively (p < 0.001). Pair-wise comparison of ipi/nivo vs PD-1i favored ipi/nivo (OS p = 0.059) despite a greater proportion of pts with M1d disease (24% vs 15%; p = 0.012). The benefit of ipi/nivo was more pronounced in pts < 65 y (5 y OS 45% vs 36%; p = 0.07), but less clear in pts ≥ 65 y (5 y OS 40% vs 36%; p = 0.385). An OS benefit was observed with ipi/nivo in pts with BRAF wild-type disease (5 y 47.5% vs 33%, p = 0.018 (cutaneous/unknown only, p = 0.021) but not in patients with BRAFmut positive disease (5 y 38% vs 41.5%, p = 0.989). Those treated with ipi/nivo vs PD-1i had numerically higher rates of CR (37% vs 26%), though pts who achieved a CR with either ipi/nivo or PD-1i had a similar 5 y OS (88% vs 96%; p = 0.285). To minimize guarantee-time bias, a 1 y landmark analysis was performed for those treated with ipi/nivo and PD-1i, excluding pts that died during the first year. 5 y OS differed significantly by response (CR, PR, SD, PD) to both ipi/nivo (86%, 36.5%, 42%, 8%; p < 0.001) and PD-1i (90.5%, 35%, 16%, 19%; p < 0.001). Conclusions: Overall, pts treated with ipi/nivo have the best long-term outcomes. However, outcomes are similar in pts treated with PD-1i who have a CR. Further, in older pts and pts with BRAFmut positive disease the benefit of ipi/nivo over PD-1i is less clear.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".