AstraZeneca demonstrated the significant findings from the SERENA...

Camizestrant (AZD9833) is an oral SERD that has shown antitumor efficacy in a range of preclinical models of breast cancer. This compound was a highly potent SERD that showed a pharmacological profile comparable to fulvestrant’s ability to degrade ERα in both MCF-7 and CAMA-1 cell lines. Stringent control of lipophilicity ensured it had favorable physicochemical and preclinical pharmacokinetic properties for oral administration. As per the findings presented at the ASCO 2023 conference, around 48/147 (32.7%) patients treated with camizestrant and 35/73 (47.9%) treated with fulvestrant had a detectable ESR1m in at least one baseline sample.

The table below shows the full analysis of progression-free survival (PFS) in pooled camizestrant cohorts.

Pooled camizestrant versus fulvestrant in the full analysis set
	Camizestrant 75 mg + 150 mg (n=147)	Fulvestrant 500 mg (n=73)
Events, n (%)	101 (68.7)	58 (79.5)
PFS, median (90%CI), months	7.4 (5.5–9.5)	3.7 (2.0–6.0)
Adjusted Hazard ratio (90%CI)	0.62 (0.47–0.82)	–

The next table represents the PFS by the presence of ESR1m at baseline in pooled camizestrant cohorts.

Pooled camizestrant versus fulvestrant, ESR1m detected
	Camizestrant 75 mg + 150 mg (n=48)	Fulvestrant 500 mg (n=35)
Events, n (%)	37 (77.1)	31 (88.6)
PFS, median (90%CI), months	8.0 (4.5–12.0)	2.2 (1.9–3.8)
Adjusted Hazard ratio (90%CI)	0.44 (0.28–0.68)	–

This table provides insights where ESR1m is not detected.

Pooled camizestrant versus fulvestrant, ESR1m not detected
	Camizestrant 75 mg + 150 mg (n=97)	Fulvestrant 500 mg (n=37)
Events, n (%)	62 (63.9)	26 (70.3)
PFS, median (90%CI), months	6.1 (3.8–9.5)	7.2 (2.0–10.7)
Adjusted Hazard ratio (90%CI)	0.79 (0.54–1.19)	–

Patients with ESR1m exhibited shorter median PFS in the fulvestrant control group compared to those without detectable ESR1m.

The below table explains the PFS by number of ESR1m detected

ESR1m , 1 variant detected
	Camizestrant 75 mg + 150 mg (n=21)	Fulvestrant 500 mg (n=17)
Events, n (%)	15 (71.4)	15 (88.2)
PFS, median (90%CI), months	12.9 (4.5–14.7)	2.2 (1.9–9.3)
Adjusted Hazard ratio (90%CI)	0.52 (0.28–0.97)	–

KOL insights

“Camizestrant demonstrated a statistically significant and clinically meaningful benefit versus fulvestrant in progression-free survival (PFS) in the overall study population.” –Expert Opinion.

“Novel SERDs: where are we? One agent approved (elacestrant) with positive phase 3 data and clinically meaningful PFS among patients with ESR1-mutant & endocrine-sensitive tumors. Promising randomized data (ph2) also with camizestrant. No benefit with girerestrant or amcenestrant.”–Expert Opinion

Conclusion- Camizestrant shines with profound significance and statistical superiority over fulvestrant in progression-free survival across the entire study cohort. However, a pioneering exploration with restricted sample sizes in certain ESR1m subgroups poses challenges in firmly concluding from the data. Lastly, the singular ESR1m patients witness remarkable enhancement in median PFS, paving the way for early intervention with camizestrant to unleash optimal benefits. The SERENA-6 clinical trial (NCT04964934) explores this hypothesis with great promise