Abstract P5-21-03: Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups
Bibliographic record
Abstract
Abstract BACKGROUND: Endocrine therapy (ET) has been the primary first-line (1L) therapy for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL (P)+LET (L) significantly prolonged progression-free survival (PFS; HR=0.58, P<.001) after a median 23 mo follow-up (FU) (Finn et al. NEJM 2016). Here we report more mature PFS overall and in subgroups, with (w/) longer FU. The study is ongoing for overall survival FU. METHODS: Postmenopausal pts w/ ER+/HER2- ABC and no prior systemic therapy in the ABC setting were randomized 2:1 to P (125 mg/d) + L (2.5 mg QD) or placebo (PBO) + L. Key endpoints: investigator-assessed PFS and safety. Median PFS (mPFS) was estimated (intent-to-treat population). RESULTS: 666 pts (444, P+L; 222, PBO+L) were enrolled. Arms were well balanced: visceral (48%)/nonvisceral (52%) disease and prior ET (56%)/no prior ET (44%). After a median FU of 38 mo w/ P+L and 37 mo w/ PBO+L, mPFS was 27.6 and 14.5 mo, respectively, in the overall population (HR=0.56, P<.0001; Table). TABLE. mPFS overall and by relevant subgroupsP+LPBO+LP+L vs PBO+LmPFS, mo (95% CI)mPFS, mo (95% CI)HR (95% CI)P* Overall27.6 (22.4–30.3)14.5 (12.3–17.1)0.56 (0.46–0.69)<.0001 Measurable disease23.7 (19.3–27.6)14.5 (12.3–18.5)0.63 (0.50–0.79)<.0001 Nonmeasurable disease36.2 (27.6?NE)16.5 (8.3–19.6)0.39 (0.25–0.60)<.0001 Visceral19.3 (16.4–24.2)12.3 (8.4–16.4)0.62 (0.47–0.81)<.0005 Nonvisceral35.9 (27.7–NE)17.0 (13.8–24.8)0.50 (0.37–0.67)<.0001 Bone only†36.2 (27.6–NE)11.2 (8.2–22.0)0.41 (0.26–0.63)<.0001 Not bone only24.2 (19.4–27.7)14.5 (12.9–18.5)0.62 (0.50–0.78)<.0001 De novo metastatic27.9 (22.1–33.4)22.0 (13.9–27.4)0.61 (0.44–0.85)<.005 Prior ET24.2 (18.8–27.6)11.2 (8.4–14.5)0.54 (0.42–0.71)<.0001 No prior ET30.3 (24.5–35.7)21.9 (15.9–27.4)0.59 (0.43–0.80)<.0005 Nonvisceral36.2 (27.9–NE)27.6 (19.1–35.6)0.59 (0.38–0.92)<.01 Visceral23.7 (16.8–30.3)13.9 (10.2–22.2)0.55 (0.36–0.85)<.005 Disease sites130.4 (24.8–NE)16.5 (11.0–22.1)0.52 (0.36–0.75)<.0005228.1 (19.4–NE)16.3 (11.0–27.4)0.57 (0.37–0.89)<.01323.7 (19.2–27.6)13.8 (8.8–17.0)0.61 (0.46–0.82)<.0005NE=not estimable. *Not adjusted for multiple analyses; 1-sided P values. †Per tumor site. All subgroups benefited from addition of P to L. Notably, pts w/ low disease burden (bone only, nonvisceral disease, few disease sites) derived significant PFS benefit, including those w/ both nonvisceral disease and no prior ET (mPFS, 36.2 vs 27.6 mo; HR=0.59, P<.01). Importantly, median time from randomization to start of 2nd subsequent systemic anticancer therapy was 39 vs 29 mo for P+L vs PBO+L (HR=0.72, P<.005). There were no new safety signals w/ longer FU. CONCLUSIONS: This is the longest FU of a phase 3 study of a cyclin-dependent kinase 4/6 inhibitor for ABC. P+L continues to consistently improve PFS vs PBO+L across all subgroups while toxicity remains manageable; notably P+L delays time to starting 2nd subsequent anticancer therapies by 10 mo. Pts w/ low disease burden or sensitivity to ET alone had PFS >3 y (significant vs PBO+L), demonstrating the clinical benefit of P+ET. These data confirm P+L should be a 1L therapy option for pts w/ HR+/HER2- ABC. Funding: Pfizer Citation Format: Rugo HS, Finn RS, Dieras V, Ettl J, Lipatov O, Joy A, Harbeck N, Castrellon A, Lu DR, Mori A, Gauthier ER, Huang C, Gelmon KA, Slamon DJ. Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-03.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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 teacher head, 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".