Table 1.
Changes in biomarker expression with treatment.
| Ki67 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 81 | −83.0 | −87.8 to −76.2 | <0.001 | 64 | −30.1 | −49.8 to −2.6 | 0.03 | 65 | −88.5 | −92.3 to −82.9 | <0.001 | |
| B: Let/Let+Palbo | 56 | −77.7 | −85.9 to −64.9 | <0.001 | 41 | −88.5 | −93.2 to −80.6 | <0.001 | 40 | −97.5 | −98.6 to −95.8 | <0.001 | |
| C: Palbo/Let+Palbo | 60 | −95.0 | −96.9 to −91.9 | <0.001 | 45 | −54.2 | −74.7 to −17.2 | 0.01 | 47 | −97.5 | −98.5 to −95.7 | <0.001 | |
| D: Let+Palbo/Let+Palbo | 48 | −97.1 | −98.1 to −95.7 | <0.001 | 34 | 8.0 | −29.8–65–9 | 0.72 | 38 | −97.1 | −98.5 to −94.6 | <0.001 | |
| A+B: Let (2 wk) | 137 | −81.0 | −85.5 to −75.2 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 125 | −97.4 | −98.1 to −96.4 | <0.001 | |||||||||
| A+B vs. C | <0.001 | A vs. B | <0.001 | A vs. B+C+D | <0.001 | ||||||||
| A+B vs. D | <0.001 | A vs. C | 0.19 | ||||||||||
| C vs. D | 0.15 | A vs. D | 0.06 | ||||||||||
| c-PARP | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 70 | −9.9 | −23.8–6.6 | 0.22 | 48 | −34.3 | −46.6 to −19.1 | <0.001 | 47 | −31.4 | −46.9 to −11.5 | 0.005 | |
| B: Let/Let+Palbo | 51 | −26.4 | −39.4 to −10.7 | 0.003 | 31 | −48.7 | −59.7 to −34.7 | <0.001 | 33 | −59.9 | −69.3 to −47.6 | <0.001 | |
| C: Palbo/Let+Palbo | 50 | −37.4 | −48.3 to −24.2 | <0.001 | 37 | −25.8 | −42.8 to −3.6 | 0.03 | 37 | −56.0 | −66.4 to −42.5 | <0.001 | |
| D: Let+Palbo/Let+Palbo | 39 | −24.4 | −37.4 to −8.8 | 0.005 | 23 | −28.6 | −42.6 to −11.3 | 0.004 | 28 | −54.0 | −65.6 to −38.5 | <0.001 | |
| A+B: Let (2 wk) | 121 | −17.3 | −27.1 to −6.1 | 0.004 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 98 | −56.8 | −63.0 to −49.7 | <0.001 | |||||||||
| A+B vs. C | 0.03 | A vs. B | 0.09 | A vs. B+C+D | 0.001 | ||||||||
| A+B vs. D | 0.45 | A vs. C | 0.51 | ||||||||||
| C vs. D | 0.34 | A vs. D | 0.61 | ||||||||||
| RB1 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 79 | −13.4 | −23.7 to −1.8 | 0.03 | 63 | −17.5 | −36.0–6.4 | 0.14 | 65 | −23.8 | −38.9 to −4.9 | 0.02 | |
| B: Let/Let+Palbo | 54 | −25.4 | −40.5 to −6.4 | 0.01 | 39 | 16.3 | −17.8–64.6 | 0.38 | 36 | −22.8 | −34.7 to −8.7 | 0.004 | |
| C: Palbo/Let+Palbo | 56 | 7.9 | −6.5–24.4 | 0.29 | 39 | −25.0 | −42.6 to −2.0 | 0.04 | 42 | −19.1 | −42.8–14.6 | 0.23 | |
| D: Let+Palbo/Let+Palbo | 49 | −16.1 | −31.9–3.4 | 0.1 | 32 | −23.1 | −52.5–24.6 | 0.28 | 38 | −39.9 | −60.4 to −9.0 | 0.02 | |
| A+B: Let (2 wk) | 133 | −18.5 | −27.5 to −8.3 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 116 | −27.7 | −40.1 to −12.6 | <0.001 | |||||||||
| A+B vs. C | 0.005 | A vs. B | 0.16 | A vs. B+C+D | 0.04 | ||||||||
| A+B vs. D | 0.57 | A vs. C | 0.23 | ||||||||||
| C vs. D | 0.004 | A vs. D | 0.99 | ||||||||||
| ER | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 81 | −4.2 | −8.5–0.3 | 0.07 | 67 | −1.9 | −6.3–2.7 | 0.41 | 66 | −4.9 | −9.3 to −0.3 | 0.04 | |
| B: Let/Let+Palbo | 56 | 13.6 | −13.6–49.5 | 0.35 | 37 | −1.9 | −8.3–4.9 | 0.57 | 35 | 1.2 | −9.5–13.1 | 0.83 | |
| C: Palbo/Let+Palbo | 59 | 0.9 | −3.9–5.9 | 0.72 | 42 | −11 | −22.9–2.8 | 0.11 | 43 | −9.8 | −23.4–6.3 | 0.21 | |
| D: Let+Palbo/Let+Palbo | 50 | −3.2 | −6.0 to −0.3 | 0.03 | 32 | −3.1 | −7.9–1.9 | 0.21 | 36 | −8.1 | −13.1 to −2.8 | 0.004 | |
| A+B: Let (2 wk) | 137 | 2.7 | −8.3–15.2 | 0.64 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 114 | −6.0 | −12.5–1.0 | 0.09 | |||||||||
| A+B vs. C | 0.64 | A vs. B | 0.81 | A vs. B+C+D | 0.91 | ||||||||
| A+B vs. D | 0.36 | A vs. C | 0.37 | ||||||||||
| C vs. D | 0.30 | A vs. D | 0.53 | ||||||||||
| PgR | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 75 | −87.1 | −92.8 to −76.8 | <0.001 | 63 | −76.1 | −87.0 to −56.2 | <0.001 | 64 | −96.9 | −98.4 to −93.8 | <0.001 | |
| B: Let/Let+Palbo | 55 | −89.0 | −94.2 to −79.2 | <0.001 | 39 | −57.6 | −80.2 to −9.2 | 0.03 | 39 | −95.8 | −98.3 to −89.5 | <0.001 | |
| C: Palbo/Let+Palbo | 56 | −11.5 | −50.1–56.9 | 0.67 | 40 | −87.1 | −94.3 to −70.4 | <0.001 | 41 | −87.1 | −94.9 to −67.7 | <0.001 | |
| D: Let+Palbo/Let+Palbo | 50 | −88.3 | −94.3 to −75.9 | <0.001 | 37 | −75.5 | −87.2 to −53.4 | <0.001 | 40 | −97.4 | −98.9 to −93.7 | <0.001 | |
| A+B: Let (2 wk) | 130 | −87.9 | −92.1 to −81.5 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 120 | −94.8 | −96.9 to −91.2 | <0.001 | |||||||||
| A+B vs. C | <0.001 | A vs. B | 0.76 | A vs. B+C+D | 0.31 | ||||||||
| A+B vs. D | 0.69 | A vs. C | 0.09 | ||||||||||
| C vs. D | <0.001 | A vs. D | 0.30 | ||||||||||
| CCNE1 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 75 | −63.6 | −74.0 to −49.0 | <0.001 | 63 | −18.6 | −49.4–30.8 | 0.39 | 64 | −68.2 | −78.5 to −52.9 | <0.001 | |
| B: Let/Let+Palbo | 54 | −61.8 | −76.6 to −37.6 | <0.001 | 39 | −45.7 | −68.3 to −7.0 | 0.03 | 38 | −82.9 | −91.2 to −67.0 | <0.001 | |
| C: Palbo/Let+Palbo | 57 | −47.1 | −63.8 to −22.7 | 0.001 | 42 | −24.2 | −60.0–43.7 | 0.39 | 42 | −64.8 | −78.3 to −42.9 | <0.001 | |
| D: Let+Palbo/Let+Palbo | 45 | −68.1 | −78.5 to −52.6 | <0.001 | 28 | −2.6 | −45.9–75.2 | 0.93 | 33 | −73.9 | −85.9 to −51.7 | <0.001 | |
| A+B: Let (2 wk) | 129 | −62.9 | −71.9 to −50.9 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 113 | −74.7 | −81.8 to −64.7 | <0.001 | |||||||||
| A+B vs. C | 0.06 | A vs. B | 0.90 | A vs. B+C+D | 0.51 | ||||||||
| A+B vs. D | 0.45 | A vs. C | 0.61 | ||||||||||
| C vs. D | 0.04 | A vs. D | 0.50 | ||||||||||
| CCND1 (IHC) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 77 | −66.0 | −77.9 to −47.5 | <0.001 | 62 | −58.2 | −75.8 to −27.6 | 0.002 | 63 | −80.9 | −87.6 to −70.8 | <0.001 | |
| B: Let/Let+Palbo | 54 | −67.8 | −81.7 to −43.3 | <0.001 | 34 | −14.7 | −49.8–44.8 | 0.54 | 35 | −67.6 | −82.6 to −39.7 | 0.001 | |
| C: Palbo/Let+Palbo | 57 | 28.7 | −3.1–71.1 | 0.08 | 40 | −70.1 | −83.7 to −45.1 | <0.001 | 43 | −64.5 | −81.1 to −33.4 | 0.002 | |
| D: Let+Palbo/Let+Palbo | 46 | −58.9 | −74.0 to −35.1 | <0.001 | 35 | −46.2 | −74.4–13.1 | 0.1 | 40 | −77.7 | −88.6 to −56.4 | <0.001 | |
| A+B: Let (2 wk) | 131 | −66.7 | −76.3 to −53.2 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 118 | −70.5 | −79.5 to −57.6 | <0.001 | |||||||||
| A+B vs. C | <0.001 | A vs. B | 0.06 | A vs. B+C+D | 0.01 | ||||||||
| A+B vs. D | 0.63 | A vs. C | 0.21 | ||||||||||
| C vs. D | <0.001 | A vs. D | 0.76 | ||||||||||
| CCND1 (IHC in non-amplified) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 60 | −69.3 | −81.0 to −50.3 | <0.001 | 47 | −54.7 | −76.0 to −14.4 | 0.02 | 48 | −84.7 | −90.7 to −74.7 | <0.001 | |
| B: Let/Let+Palbo | 45 | −70.2 | −84.5 to −42.8 | <0.001 | 26 | −23.1 | −54.7–30.4 | 0.32 | 28 | −71.0 | −86.0 to −40.0 | 0.002 | |
| C: Palbo/Let+Palbo | 43 | 29.1 | −10.1–85.3 | 0.16 | 32 | −73.2 | −87.2 to −43.7 | 0.001 | 35 | −65.7 | −83.4 to −29.2 | 0.005 | |
| D: Let+Palbo/Let+Palbo | 33 | −64.3 | −80.1–36.2 | 0.001 | 23 | −65.8 | −87.8 to −4.4 | 0.04 | 29 | −85.4 | −94.0 to −64.8 | <0.001 | |
| A+B: Let (2 wk) | 105 | −69.7 | −79.4 to −55.4 | <0.001 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 92 | −75.1 | −83.9–61.4 | <0.001 | |||||||||
| A+B vs. C | <0.001 | A vs. B | 0.12 | A vs. B+C+D | 0.01 | ||||||||
| A+B vs. D | 0.86 | A vs. C | 0.32 | ||||||||||
| C vs. D | <0.001 | A vs. D | 0.64 | ||||||||||
| CCND1 (IHC in amplified) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline to 2 weeks | 2 to 14 weeks | Baseline to 14 weeks | |||||||||||
| Group | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | n | Geomean Δ (%) | 95% CI | P | |
| A: Let/Let | 16 | −51.9 | −84.8–52.1 | 0.2 | 11 | −13.0 | −62.4–101.3 | 0.72 | 14 | −60.1 | −82.8 to −7.4 | 0.03 | |
| B: Let/Let+Palbo | 7 | −56.6 | −91.3–117.3 | 0.25 | 6 | 119.9 | −69.2–1467.9 | 0.35 | 5 | −11.9 | −32.7–15.4 | 0.26 | |
| C: Palbo/Let+Palbo | 14 | 27.8 | −14.6–91.3 | 0.21 | 7 | −58.7 | −85.5–17.4 | 0.08 | 8 | −58.9 | −91.3–94.2 | 0.22 | |
| D: Let+Palbo/Let+Palbo | 12 | −44.3 | −75.0–24.1 | 0.14 | 10 | 46.1 | −39.6–253.3 | 0.36 | 10 | −19.8 | −32.7 to −4.4 | 0.02 | |
| A+B: Let (2 wk) | 23 | −53.4 | −80.4–10.9 | 0.08 | |||||||||
| B+C+D: Let + Palbo (14 wk) | 23 | −35.1 | −60.0–5.2 | 0.08 | |||||||||
| A+B vs. C | 0.001 | A vs. B | 0.52 | A vs. B+C+D | 0.09 | ||||||||
| A+B vs. D | 0.59 | A vs. C | 0.02 | ||||||||||
| C vs. D | 0.01 | A vs. D | 0.39 | ||||||||||