ALPINE
The first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib.
ORR 86.2% vs 75.7%; PFS HR 0.65 (95% CI 0.49-0.86) at 29.6 months, including in del(17p)/TP53 (HR 0.53); atrial fibrillation 5.2% vs 13.3%; fewer discontinuations. NEJM 2023; 3-year update maintains PFS advantage.
Setting
Relapsed or refractory CLL/SLL: zanubrutinib vs ibrutinib
Phase
Phase 3
Sponsor
BeOne (BeiGene)
Registry
Headline result
PFS HR 0.65; AF 5.2% vs 13.3%.
Reported
2022
Enrolled
652
Replication
ELEVATE-RR (acalabrutinib vs ibrutinib) showed non-inferior PFS with less atrial fibrillation; ALPINE is the only trial to show PFS superiority.
In plain words
What these results mean for people, not percentages
Progression-free survivalprimarysurrogate endpoint
- The treated group had about 35 percent lower chance of the event at any given time (hazard ratio 0.65).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Overall response rateresponse endpoint
- 86.2 vs 75.7 out of 100 had their tumour shrink with Zanubrutinib compared with Ibrutinib; 10.5 more per 100.
- Roughly one extra person helped for every 10 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
Atrial fibrillation/flutterother endpoint
- 5.2 vs 13.3 out of 100 reached this endpoint with Zanubrutinib compared with Ibrutinib; 8.1 fewer per 100.
- On this measure the first group did worse, not better.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
Be careful
- These results apply to the people the trial enrolled: Relapsed or refractory CLL/SLL: zanubrutinib vs ibrutinib. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
652 participants enrolled.
Overall response rate
Zanubrutinib86.2 of 100
Ibrutinib75.7 of 100
Atrial fibrillation/flutter
Zanubrutinib5.2 of 100
Ibrutinib13.3 of 100
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Zanubrutinib | 327 | — | 0.65 (0.49–0.86) | 0.002 | link |
| Ibrutinib | 325 | — | ||||
| Overall response rate | Zanubrutinib | — | 86.2% | — | — | — |
| Ibrutinib | — | 75.7% | ||||
| Atrial fibrillation/flutter | Zanubrutinib | — | 5.2% | — | — | — |
| Ibrutinib | — | 13.3% |
Replication
ELEVATE-RR (acalabrutinib vs ibrutinib) showed non-inferior PFS with less atrial fibrillation; ALPINE is the only trial to show PFS superiority.