Highlights From SABCS 2022 Clinical Trial Data

Key research presented in December at the 2022 San Antonio Breast Cancer Symposium (SABCS) has the potential to inform strategies in clinical practice in the field of breast cancer. Here are some highlights of important findings.

Pausing ET to Attempt Pregnancy

Patients with breast cancer receiving endocrine therapy (ET) have often been reluctant to stop therapy to attempt getting pregnant due to fear of disease recurrence. However, results from the POSITIVE clinical trial (NCT02308085) showed that patients with breast cancer who paused ET to try to get pregnant experienced short-term rates of breast cancer recurrence similar to those of women who did not pause therapy for pregnancy, and many went on to conceive and deliver healthy babies.¹

The 3-year rate of recurrence was 8.9%, and the 3-year rate of recurrence from an external control cohort from the SOFT (NCT00066690) and TEXT (NCT00066703) trials was 9.2%, which assessed adjuvant ET in premenopausal women.²

Updates on Investigational Selective Estrogen Receptor Degraders

Fulvestrant (Faslodex; AstraZeneca) is the only FDA-approved selective estrogen receptor degrader (SERD). SERDs play an important role in the treatment of endocrine-resistant breast cancers; however, fulvestrant is only available as an intramuscular injection.

At SABCS, investigators presented data from clinical trials assessing a collection of investigational oral SERDs, including camizestrant (AZD9833; AstraZeneca) and imlunestrant (LY3484356; Eli Lilly and Company).

Camizestrant

Camizestrant is a potent, next-generation oral SERD and pure estrogen receptor α antagonist. Findings from the phase 2 SERENA-2 trial (NCT04214288) showed that the median progression-free survival (PFS) was 7.2 months with the 75-mg dose of camizestrant, 7.7 months with the 150-mg dose, and 3.7 months with fulvestrant.³

Among the prespecified subgroup of patients with ESR1 mutations, camizestrant reduced the risk of disease progression or death by 67% at the 75-mg dose (median PFS of 6.3 vs 2.2 months) and by 45% at the 150-mg dose (median PFS of 9.2 vs 2.2 months) compared with fulvestrant. A reduction in the risk of disease progression or death was also observed in patients without a detectable ESR1 mutation, with a 22% reduction in risk at the 75-mg dose and a 24% reduction in risk at the 150-mg dose.³

Camizestrant also demonstrated improved efficacy vs fulvestrant in other high-risk patient subgroups, including those with lung and/or liver metastases, who experienced a reduction in the risk of disease progression or death compared with fulvestrant. Further, patients who had been previously treated with CDK4/6 inhibitor therapy experienced a reduction in the risk of disease progression or death of 51% at the 75-mg dose and 32% at the 150-mg dose.²

Imlunestrant

Imlunestrant is an investigational oral SERD with pure antagonistic properties. The results of the EMBER-3 trial (NCT04975308), which studied imlunestrant in combination with abemaciclib (Verzenio; Eli Lilly and Company) with or without an aromatase inhibitor (AI), showed acceptable safety and tolerability comparable with that of the MONARCH 2 trial (NCT02107703) of fulvestrant plus abemaciclib and evidence of clinical activity in patients with ER+/HER2- advanced breast cancer.⁴

These data suggest no additive toxicity of imlunestrant when administered in combination with abemaciclib and a comparable clinical benefit to that observed in the MONARCH 2 trial.⁴

Investigational First-in-Class Drug

Capivasertib (AstraZeneca) is an investigational, first-in-class oral selective adenosine triphosphate (ATP)–competitive inhibitor of all 3 AKT isoforms (AKT1/2/3). It is currently in trial in combination with fulvestrant for patients with HR-positive (+)/HER2-low or negative locally advanced or metastatic breast cancer who have progressed on ET.⁵

Findings from the phase 3 CAPItello-291 clinical trial (NCT04305496) demonstrated that capivasertib plus fulvestrant doubled the median PFS compared with placebo plus fulvestrant, at 7.2 vs 3.6 months, respectively.¹

The objective response rate was 22.9% among patients treated with capivasertib plus fulvestrant vs 12.2% for patients treated with placebo plus fulvestrant. Overall, 41% of patients assigned to treatment had tumors with AKT pathway mutations.^5,6

Updated CDK4/6 Data

Abemaciclib

Adding abemaciclib to adjuvant ET can provide long-term benefits for patients with high-risk, HR+/HER2-early breast cancer, according to updated data from the monarchE trial (NCT03155997).⁷

With a median follow-up of 42 months, the benefit of abemaciclib in terms of invasive disease-free survival (IDFS) and distant relapse–free survival was maintained after patients completed 2 years of adjuvant treatment. These are encouraging results because the early benefits seen in the PENELOPE-B trial (NCT01864746) with adjuvant palbociclib (Ibrance; Pfizer) disappeared by 40 months.⁷

Ribociclib

In the phase 2 RIGHT Choice trial (NCT03839823), ribociclib (Kisqali; Novartis Pharmaceuticals Corporation) plus ET prolonged PFS by nearly 1 year compared with combination chemotherapy in pre-/postmenopausal women with HR+/HER2- breast cancer.⁸

At a median follow-up of 24.1 months, 45.5% of patients in the ribociclib-ET arm were still on treatment vs 23.6% in the chemotherapy arm. Although overall survival (OS) data were immature at the data cutoff, the median PFS was significantly longer (24.0 vs 12.3 months).⁸

Furthermore, the median time to treatment failure was significantly longer with ribociclib plus ET than with combination chemotherapy (18.6 months vs 8.5 months). The rate of treatment-related serious adverse events was 1.8% with ribociclib-ET and 8.0% with chemotherapy. The rates of treatmentrelated adverse events that led to discontinuation were 7.1% and 23.0%, respectively.⁸

Continuing CDK4/6 Inhibitors After Disease Progression

Continuing CDK4/6 inhibitor therapy and switching ET after disease progression does not improve PFS compared with switching ET alone in patients with HR+/HER2-negative (HER2–) metastatic breast cancer. The phase 2 PACE trial (NCT01207440) showed that patients who received palbociclib and fulvestrant after progression on prior CDK4/6 inhibitor therapy and ET had a PFS that was similar to that of patients who switched to fulvestrant and did not receive palbociclib.⁹

Adding avelumab (Bavencio; Pfizer) to treatment with palbociclib and fulvestrant resulted in a numeric improvement in PFS, but statistical significance was not reached. The median PFS was 4.6 months in the palbociclib/fulvestrant arm and 4.8 months in the fulvestrant alone arm, and the median OS was 24.6 months and 27.5 months, respectively.⁹

Adding Everolimus to Improve Outcomes

Adding 1 year of everolimus (Afinitor; Novartis Pharmaceuticals Corporation) to standard adjuvant ET does not improve outcomes in patients with high-risk HR+/HER2– breast cancer. The addition of everolimus did not improve IDFS or OS in the overall cohort. However, premenopausal patients did have a significant improvement in IDFS and OS with everolimus.

These findings come from SWOG S1207 (NCT01674140), a phase 3 trial designed to evaluate the role of everolimus in combination with ET in the adjuvant setting. The primary end point was IDFS.¹⁰

The 5-year IDFS rate was 74.9% among patients treated with everolimus vs 74.4% in the placebo arm. Additionally, the 5-year OS rate was 88.1% in the everolimus arm and 85.8% in the placebo arm.¹⁰

AIs vs Tamoxifen

Based on a systematic review and trilevel meta-analysis of 5 trials and a total of 7138 patients, investigators found that AIs improve DFS compared with tamoxifen citrate (Soltamox; DARA BioSciences) in patients with HR+/HER2– early breast cancer regardless of menopausal status. The median follow-up of the data ranged from 34 to 67 months, and in the pooled analysis of all 5 trials AIs were associated with a 31% reduction in the risk of recurrence or death compared with tamoxifen.¹¹

ABOUT THE AUTHOR

Douglas Braun, PharmD, CSP, RPh, is a senior pharmacy director at the American Oncology Network, LLC, in Naples, Florida.

REFERENCES

1. General session 3 includes latest results from SERENA-2, CAPItello–291, and STIC CTC trials. SABCS Meeting News. December 9, 2022. Accessed December 18, 2022. https://www.sabcsmeetingnews.org/general-session-3-includes-latest-results-from-serena-2-capitello-291-and-stic-ctc-trials/

2. McGinnis A. General session 4 includes latest results from Alliance, polar, positive studies. SABCS Meeting News. December 10, 2022. Accessed December 18, 2022. https://www.sabcsmeetingnews.org/general-session-4-includes-latest-results-from-alliance-polar-positive-studies/

3. Nye J. Camizestrant improves PFS vs fulvestrant in ER+/HER2- advanced breast cancer. Cancer Therapy Advisor. December 9, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antonio-breast-cancer-symposium-sabcs/sabcs-2022/breast-cancer-advanced-camizestrant-improves-pfs-vs-fulvestrant/

4. Lilly announces details of presentations at 2022 San Antonio Breast Cancer Symposium. Lilly Investors. November 21, 2022. Accessed December 18, 2022. https://investor.lilly.com/news-releases/news-release-details/lilly-announces-details-presentations-2022-san-antonio-breast

5. Kemp A. Capivasertib plus Faslodex reduced the risk of disease progression or death by 40% versus Faslodex in advanced HR-positive breast cancer. AstraZeneca Media. December 8, 2022. Accessed December 18, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/capivasertib-pfs-in-hr-positive-breast-cancer.html

6. General Session 3 includes latest results from SERENA-2, CAPItello–291, and STIC CTC trials. SABCS Meeting News. December 9, 2022. Accessed December 18, 2022. https://www.sabcsmeetingnews.org/general-session-3-includes-latest-results-from-serena-2-capitello-291-and-stic-ctc-trials/

7. Dembeck L. Abemaciclib provides long-term benefits in HR+, HER2- breast can cer. Cancer Therapy Advisor. December 7, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antoniobreast-cancer-symposium-sabcs/sabcs-2022/breast-cancer-hr-her2-abemaciclib-long-term-benefit

8. Dembeck L. Ribociclib plus ET outperforms chemo in HR+/HER2− advanced breast cancer. Cancer Therapy Advisor. December 8, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antonio-breast-cancersymposium-sabcs/sabcs-2022/breast-cancer-metastatic-ribociclib-endocrine-therapyoutperforms-chemo/

9. Dembeck L. Palbociclib does not improve PFS after progression on CDK4/6 inhibitors, ET. Cancer Therapy Advisor. December 9, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antonio-breast-cancer-symposium-sabcs/sabcs-2022/palbociclib-does-not-improve-pfs-after-progression-cdk4-6-inhibitors-endocrine-therapy/

10. Dembeck L. Adding everolimus to adjuvant ET does not improve survival in high-risk HR+/HER2- breast cancer. Cancer Therapy Advisor. December 7, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antonio-breast-cancer-symposium-sabcs/sabcs-2022/adding-everolimus-to-adjuvant-et-not-improve-hr-positive-her2-negative-bc/

11. Nye J. DFS improved with AIs vs tamoxifen in HR+, HER2- early breast cancer. Cancer Therapy Advisor. December 7, 2022. Accessed December 18, 2022. https://www.cancertherapyadvisor.com/home/news/conference-coverage/san-antonio-breast-cancer-symposium-sabcs/sabcs-2022/breast-cancer-hr-her2-dfs-improved-ais-vs-tamoxifen/