...approved Kisqali® (ribociclib) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage II and III early breast cancer (EBC) at high risk of recurrence...

KISQALI is a kinase inhibitor indicated for the treatment of adult patients with hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)- negative advanced or metastatic cancer in combination with...an aromatase inhibitor as initial endocrine-based therapy; or...fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy in postmenopausal women or in men.

Health Canada has approved an extended indication for KISQALI®: in combination with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy, as well as in combination with an aromatase inhibitor (and luteinizing hormone releasing hormone [LHRH] agonist) for the treatment of pre/perimenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy.

SMC has accepted ribociclib for the treatment of advanced HR-positive, HER2-negative breast cancer, in combination with fulvestrant...

ribociclib (Kisqali®) is accepted for use within NHS Scotland....In combination with an aromatase inhibitor, for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer as initial endocrine-based therapy.

KISQALI is a kinase inhibitor indicated in combination with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy...or... fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrinebased therapy or following disease progression on endocrine therapy.

Ribociclib plus fulvestrant is recommended as an option for treating hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer in adults who have had previous endocrine therapy...

HER2 Negative Breast Cancer: Invasive Breast Cancer…SYSTEMIC THERAPY FOR ER - AND/OR PR - POSITIVE RECURRENT OR STAGE IV (M1) DISEASE…HER2-Negative and Postmenopausal or Premenopausal Receiving Ovarian Ablation or Suppression…Preferred Regimens...Fulvestrant+ CDK4/6 inhibhitor ( Abemaciclib, palbociclib or ribociclib) (Category 1)

...patients with stage II and III HR+/HER2− early breast cancer...RIB + NSAI demonstrated a significant iDFS benefit over NSAI alone (HR, 0.749; 95% CI, 0.628-0.892; P=.0006). The 3-year iDFS rates were 90.7% (95% CI,89.3%-91.8%) vs 87.6% (95% CI, 86.1%-88.9%)….With a substantial proportion of patients completing 3 years of RIB treatment, NATALEE continues to demonstrate a significant iDFS improvement with RIB + NSAI over NSAI alone.

At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50-0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo....This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2- ABC.

Ribociclib added to standard-of-care ET demonstrated a statistically significant, clinically meaningful improvement in iDFS with a well-tolerated safety profile. The NATALEE results support ribociclib + ET as the treatment of choice in a broad population of pts with stage II or III HR+/HER2− EBC, including pts with N0 disease.

Novartis today announced positive topline results from an interim analysis of NATALEE, a Phase III trial evaluating Kisqali® (ribociclib) plus endocrine therapy (ET) in a broad population of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) at risk of recurrence...

This phase 4, prospective, noninterventional study included pts with HR+, HER2− ABC treated with RIB+AI...Median PFS was 20.6 months (95% CI, 17.5-NE)….Clinical outcomes with RIB+AI were found to be consistent with MONALEESA-2.

CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC….Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2- ABC, including populations of interest (NCT02941926).

Overall, 3.4% of patients experienced a CR and 43.3% a PR. ORR and CBR were higher for patients aged <50 years than for those aged ≥50 years....Overall, these findings support the efficacy and manageable safety profile of ribociclib in combination with letrozole as first-line treatment in a population of Spanish patients with HR+/HER2− ABC approaching that of a real-world setting.

Patients with HR+, HER2- ABC received ribociclib (600 mg/day, 3 weeks on/1 week off) plus letrozole (2.5 mg/day)...The overall response rate was 28.2 % (95 % confidence interval [CI], 24.4-32.1); clinical benefit rate was 71.7 % (95 % CI, 67.7-75.4); and median time to progression was 26.7 months (95 % CI, 24.8-non-estimable)....The safety and efficacy profiles of ribociclib plus letrozole in the Italian subpopulation was found to be consistent with the CompLEEment-1 global population result, MONALEESA-2, and MONALEESA-7 outcomes, which reaffirm ribociclib plus letrozole as the frontline treatment option in patients with HR+, HER2- ABC.

mOS was 66.0 (95% CI, 57.6-75.7) mo in pts with ≥ 1 RIB dose reduction vs 60.6 (95% CI, 42.5-79.2) mo in pts with no RIB dose reductions (HR, 0.87 [95% CI, 0.65-1.18])….In this exploratory analysis of ML-2, OS benefit was maintained in pts with HR+/HER2− ABC who required mod from the recommended starting dose of RIB (600 mg/d 3 wk on/1 wk off).

This exploratory analysis of 1L RIB + FUL in MONALEESA-3 reports the longest mOS thus far (67.6 mo—a 15.8-mo improvement vs PBO and a relative reduction in risk of death of 33%) in a 1L population in a Phase III clinical trial in ABC. These impressive results in the 1L setting further support the use of RIB + ET in HR+/HER2− ABC.

All primary and subsequent reports of RCTs of first-line systemic treatments for HR-positive, ERBB2-negative MBC that were referenced...Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third....In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC.

Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third....In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC.

In updated biomarker and clinical subgroup analyses from the phase III MONALEESA trials, ribociclib demonstrated consistent improvements in overall survival when added to endocrine therapy in patients with HR-positive/HER2-negative advanced breast cancer.

Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, 47.2 to 59.7) with placebo plus letrozole (hazard ratio for death, 0.76; 95% CI, 0.63 to 0.93; two-sided P = 0.008)....First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer.

Patients with HR+, HER2- ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous)....Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population....These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.

Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years)....R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS.

RIB + LET showed a significant OS benefit vs PBO + LET (median, 63.9 vs 51.4 mo; HR, 0.76; 95% CI, 0.63-0.93; P=.004) and met the boundary of statistical significance. Estimated 6-year OS rate was 44.2% for RIB vs 32.0% for PBO….To date, this is the first report of a statistically significant and clinically meaningful OS benefit with a 1L CDK4/6i in postmenopausal pts with HR+/HER2– ABC. After a median follow-up of >6.5 y, median OS improvement was >12 mo for 1L RIB + LET vs PBO + LET.

RIBECCA was a phase 3b, multicentre, open-label study of RIB + LET in patients (pts) of any menopausal status with HR+, HER2–ABC, who were not amenable to curative treatment (tx)….In cohort B1 (n=26), confirmed CBR was (57.7% [95% CI, 36.9-76.6], ORR at week 24 was 23.1% (95% CI, 9.0-43.6) and median PFS was 16.5 months (mo; 95% CI, 3.2-not calculable). In cohort B2 (n=154), confirmed CBR was 56.5% (95% CI, 48.3-64.5), ORR at week 24 was 11.7% (95% CI, 7.1-17.8) and median PFS was 8.8 mo (95% CI, 8.1-16.3)....The data confirmed the clinical and PFS benefit of RIB + LET in both cohorts B1 and B2.

Postmenopausal patients with HR+/HER2− ABC were randomized 1:1 to receive first-line RIB or PBO with LET... Consistent with the intent-to-treat population of ML-2, the results of this prespecified exploratory analysis demonstrated an OS benefit with RIB + LET independent of the site and number of metastatic lesions.

In summary, with demonstrated benefits in OS, time to subsequent therapy, and PFS2, long-term follow-up data from the MONALEESA-3 trial illustrate the role of ribociclib plus fulvestrant in changing the natural history of HR-positive, HER-negative advanced breast cancer...

...the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88 months). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04 months)...This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2− ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.

The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC.

This analysis reported extended OS follow-up in MONALEESA-3. mOS was ≈12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.

...pts with HR+/HER2− ABC with no prior CDK4/6i or ET for ABC were randomized 1:1 to receive RIB or PBO plus goserelin and a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen…RIB + ET demonstrated an OS benefit vs PBO + ET (median, 51.3 vs 40.5 mo; HR, 0.65; 95% CI, 0.43-0.98....In ML-7, RIB prolonged OS and improved post-progression outcomes in HR+/HER2− ABC.

Taken together, these findings demonstrate the potential clinical utility of intrinsic tumor subtype as a biomarker in patients with HR‐positive/HER2‐negative advanced breast cancer. Patients with HER2‐enriched tumors experienced the greatest magnitude of improvement in PFS when treated with ribociclib...

These findings indicate that treatment with RIB + NSAI improved PFS nearly 3-fold and prolonged OS with a relative reduction in risk of death of 56% vs PBO + NSAI in Asian pts with HR+/HER2− ABC.

Patients with HR+, HER2- ABC, ≤1 line of prior chemotherapy (CT), and no prior ET in the advanced setting, received ribociclib + letrozole...The overall response rate was 25.9% (95% CI: 18.8, 34.0) and clinical benefit rate was 74.1% (95% CI: 66.0, 81.2)...

Pts received RIB (600 mg QD, 3 weeks on/1 week off) in combination with LET (2.5 mg QD, continuous). For the 32 patients with measurable disease, ORR was 46.9% (95% CI, 29.1-65.3%) and CBR was 71.9% (95% CI, 53.3-86.3)...efficacy results support the use of RIB + LET in HR+, HER2- ABC in a close to real-world setting.

Patients with HER2E (hazard ratio [HR], 0.389; P < .0001), LumB (HR, 0.521; P = .0001), LumA (HR, 0.633; P = .0007), and normal-like (HR, 0.467; P = .0005) subtypes all derived benefit from RIB treatment,...Patients with HER2E, LumA, LumB, and normal-like subtypes all exhibited a consistent PFS benefit with RIB treatment, while patients with basal-like ABC (RIB: 2%; PBO: 3%) did not. The HER2E subtype (RIB: 14%; PBO: 11%) exhibited the greatest relative reduction in risk of progression or death (61%) with RIB plus ET.

These findings indicate that treatment with RIB + NSAI improved PFS nearly 3-fold and prolonged OS with a relative reduction in risk of death of 56% vs PBO + NSAI in Asian pts with HR+/HER2− ABC.

Pre- or perimenopausal patients with HR+/HER2− ABC were randomized 1:1 to receive RIB or PBO plus goserelin with either a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole) or tamoxifen...."These updated results with extended follow-up demonstrated an OS benefit with RIB + ET vs PBO + ET (median, 58.7 vs 48.0 mo; HR, 0.76 [95% CI, 0.61-0.96]). In patients receiving an NSAI, a similar OS benefit was observed with RIB + NSAI vs PBO + NSAI (median, 58.7 vs 47.7 mo; HR, 0.80 [95% CI, 0.62-1.04])."

...167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6%) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant....Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor–positive, HER2-negative advanced breast cancer.

Pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy, and no prior ET for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6-mg subcutaneous implant every 28 days)...Preliminary results from the CompLEEment-1 study demonstrate the safety and tolerability of first-line RIBO+LET+goserelin in male pts, consistent with previous reports in female pts.

A total of 668 postmenopausal women with HR+, HER2– recurrent/metastatic breast cancer were randomized...to ribociclib...plus letrozole...The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease....The improved efficacy outcomes and manageable tolerability observed with first-line ribociclib plus letrozole are maintained with longer follow-up, relative to letrozole monotherapy.

672 pts with ≤1 line of prior CT and no prior ET for ABC were randomized 1:1 to RIB (600 mg/day, 3-weeks-on/1-week-off) or PBO + TAM (20 mg/day) or an NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) and goserelin (3.6 mg every 28 days)....consistent treatment benefit with RIB + TAM/NSAI vs PBO + TAM/NSAI was observed in premenopausal pts with HR+, HER2– ABC, regardless of prior CT for ABC.

The MONALEESA-7 trial (NCT02278120) investigated ribociclib (or placebo) + a nonsteroidal aromatase inhibitor or tamoxifen + goserelin ovarian suppression in premenopausal women with ≤1 line of prior chemotherapy for ABC (N = 672); 40% had de novo ABC. Median progression-free survival (PFS) was 23.8 vs 13.0 months with ribociclib (n = 335) vs placebo (n = 337)...safety and efficacy established in the MONALEESA-7 trial of premenopausal women and premenopausal subsets of the PALOMA-3 and MONARCH 2 trials support using CDK4/6 inhibitor combination therapy in these patients.

PFS was significantly improved in the RIB arm vs the PBO arm (hazard ratio: 0.593; 95% confidence interval [CI]: 0.480–0.732; p = 4.10×10–7); median PFS: 20.5 months; 95% CI: 18.5–23.5 vs 12.8 months; 95% CI: 10.9–16.3....RIB + FUL vs PBO + FUL significantly prolonged PFS and demonstrated a manageable safety profile in postmenopausal pts with HR+, HER2– ABC who received no or up to 1 line of prior ET for advanced disease. 

Novartis today announced Kisqali (ribociclib) received US Food and Drug Administration (FDA) Breakthrough Therapy designation for initial endocrine-based treatment of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.

Estimated OS rates with RIB + ET vs PBO + ET at 42 mo were 70.2% vs 46.0%, respectively. In pts who received an NSAI (n=495), RIB + ET demonstrated a consistent OS improvement vs PBO + ET (HR, 0.699 [95% CI, 0.50-0.98]).

Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2− advanced breast cancer in the first-line setting.

Patients also received either a nonsteroidal aromatase inhibitor (letrozole at a dose of 2.5 mg or anastrozole at a dose of 1 mg) or tamoxifen (at a dose of 20 mg), administered orally once daily continuously....randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen)....The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98).

...- Histologically or cytologically confirmed diagnosis of HR-positive (ER+ ≥10%), HER2-negative advanced stage breast cancer...

...The investigator must confirm postmenopausal statusPostmenopausal status is defined either by- Age ≥ 55 years and one year or more of amenorrhea- Age < 55 years and one year or more of amenorrhea and postmenopausal levels of FSH and LH- Prior hysterectomy and has postmenopausal levels of FSH and LH- Surgical menopause with bilateral oophorectomyEverolimus cohort:• Cholesterol ≤ 2.0 × ULNRibociclib cohort:• Standard 12-lead ECG values assessed by the local laboratory:- QTcF interval at screening < 450 msec (us-ing Fridericia’s correction)- Resting heart rate 50-90 bpm• INR ≤ 1,5 (ribocilclib cohort)• Patients must have the following laboratory values within normal limits or corrected to within normal limits with supplemets before the first dose of study medication:-Sodium-Potassium-Total calcium Eribulin cohort (DIVb)• Either hormone-receptor negative MBC or hormone-receptor positive MBC with indication for chemotherapy• Up to three previous chemotherapy treatment lines for metastatic disease• In case of patients of child bearing potential:- Negative pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 7 days prior to recruitment- Contraception by means of a reliable method (i.e. non-hormonal contraception, IUD, a double barrier method, vasectomy of the sexual partner, complete sexual abstinence). ...

...Histologically or cytologically confirmed diagnosis of hormone receptor positive (ER+ ≥10%), HER2 negative, metastatic breast cancer.2. ...

...- Histologically confirmed unresectable, locally advanced or metastatic invasive breast cancer with hormone receptor positive/HER2 negative...

Eligible studies included randomized controlled trials (RCTs) assessing endocrine therapy alone or in combination with CDK4/6i as first-line endocrine treatment for HR+/HER2- ABC patients....Considering OS, the top three ranked treatments were ribociclib+fulvestrant (SUCRA = 94.1%), abemaciclib+NSAI (SUCRA = 69.9%), and ribociclib+NSAI (SUCRA = 68.5%)….Ribociclib+fulvestrant probably represents the best option in a first-line setting. When combined with NSAI, dalpiciclib likely showed the best efficacy but the worst safety.

A single-institution study analyzed retrospective data from 108 patients treated with palbiciclib or ribociclib with endocrine therapy in first-line in HR+/HER2– MBC patients at Ho Chi Minh city oncology hospital….The PFS rates at 6, 12 and 18 months were 94.4%, 93.5% and 91.5%, respectively.

Our results are in line with the recently published phase 2 clinical trial RIGHT CHOICE, which showed a prolonged progression free survival in patients treated with ribociclib and HT with HR+/HE2- ABC and visceral crisis.

Data were pooled from the MONALEESA-2, -3, and -7 trials of pre- and postmenopausal pts with HR+/HER2− ABC treated with first-line RIB + ET or placebo (PBO) + ET….This pooled analysis of the MONALEESA-2, -3, and -7 trials demonstrated PFS and OS benefits with RIB + ET in elderly pts consistent with those observed in younger pts. Across age subgroups, treatment with RIB + ET also delayed TTC.

In Asian pts, the overall response rate (ORR) was higher with RIB + ET than CT, with similar clinical benefit rate (CBR) and median time to response (mTTR) in both arms. In non-Asian pts, the ORR and CBR were similar in both arms, with longer mTTR for RIB + ET vs CT....This post hoc analysis confirmed a clinically meaningful PFS benefit with 1L RIB + ET vs combo CT in pre- or perimenopausal Asian and non-Asian pts with HR+/HER2− ABC.

Patients with HER2E (HR, 0.60; P=.018), luminal B (HR, 0.69; P=.023), and luminal A (HR, 0.75; P=.021) subtypes derived OS benefit with ribociclib….The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest data set in HR+/HER2- ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.

The data of patients with bone marrow-involved hormone receptor-positive (HR+) Her2-negative mBC between 2019- 2022 who received ribociclib or palbociclib in combination with endocrine therapy (ET) were retrospectively analyzed within the thirteen centers....When the CDKi response was evaluated, 2 (8.7%) of the patients had a complete response, 11 (47.8%) had a partial response, 8 (34.8%) had stable disease, and 2 (8.7%) had progressive disease….It has been shown that PFS similar to those in randomized clinical studies can be achieved with CDK 4/6 inhibitors combined with ET in treating hormone receptor-positive Her2-negative bone marrow-involved metastatic breast cancer.

Retrospective-prospective study of Portuguese cohort adult women with HR+/HER2- ABC treated with ribociclib through 3 years….At 12 months, complete response was achieved in 15 patients (5.6%), 80 patients (29.6%) had partial response and 52 (19.3%) remained stable.

Pre/perimenopausal pts (N=222) with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT....In pts with visceral crisis, a mPFS of 12.9 mo was seen with RIB + ET vs 11.2 mo with combo CT (HR, 0.87). While in these pts the overall response rate (ORR) numerically favored RIB + ET, the time to treatment failure (TTF) and clinical benefit rate (CBR) were similar in both tx arms...This analysis shows similar PFS and TTF outcomes but greater ORR with RIB + ET vs combo CT in pts with physician-assessed visceral crisis.

Median PFS was 12.4 months [95% CI 8.7-24.4] for patients who received ribociclib + ET and 4.75 months [95% CI 1.0-10.3] for those who received ET only….The results of the AMICA study show a promising efficacy and safety of maintenance treatment with ribociclib added to ET after at least stable disease following the first metastatic chemotherapy in patients with HR+/HER2-mBC.

A total of 43 patients received ribociclib + ET and 10 patients received ET only. Median PFS was 12.4 months [95% CI 8.7-24.4] for patients who received ribociclib + ET and 4.75 months [95% CI 1.0-10.3] for those who received ET only….The results of the AMICA study show a promising efficacy and safety of maintenance treatment with ribociclib added to ET after at least stable disease following the first metastatic chemotherapy in patients with HR+/HER2-mBC.

Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%)....For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%)….Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients.

There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo....In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2– MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

This analysis demonstrated a clinically meaningful PFS benefit and improved secondary outcomes with 1L RIB + ET over combo CT along with similar treatment responses in both tx arms in pts aged < 40 y as well as in those ≥ 40 y with aggressive HR+/HER2− ABC.

The unadjusted KM estimate for median PFS was 32.2 months (95% CI, 29.3–34.8) in the RIB + AI/FUL cohort, 35.2 months (95% CI, 23.9–44.2) in the ET cohort, and 16.7 months (95% CI, 9.9–17.5) in the CT cohort. Multivariate analysis showed that PFS was independently affected by several baseline parameter. After CPHR Analysis RIB + AI/FUL was associated with prolonged PFS compared with ET or CT.

There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo....In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

The objective was to compare ribociclib versus CDK4/6 inhibitors and ET in patients with the 1L pre/post-menopausal HR+/HER2-metastatic/advanced breast cancer patients in Asia....Favorable OS was associated with ribociclib plus AI versus AI alone (HR: 0.64 [0.35,1.17]), while results were comparable against abemaciclib plus AI (HR: 1.01 [0.45, 2.24])....Ribociclib was associated with significant PFS benefit against palbociclib in post-menopausal patients and was comparable or numerically better against other CDK4/6 inhibitors (abemaciclib and dalpiciclib) among pre-/post-menopausal patients.

In the preM cohort, the median PFS was 27.6 vs 14.7 mo (HR 0.672; 95% CI 0.448-1.009) for RIB vs PBO. ORR was higher for RIB in both postM and preM pts...Along with the results of the ML studies, this bridging study demonstrates the consistent efficacy benefit and well-tolerated safety profile of RIB + ET in Chinese pts.

In our study, we found that CDK 4-6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4-6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

Response and clinical benefit rates were particularly encouraging compared with those of the ribociclib group of MONALEESA-7. Our work confirms that ribociclib in combination with endocrine therapy is highly effective in the treatment of premenopausal HR+/HER2- advanced breast cancer patients with an expected safety profile.

KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC....The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS (>36.5 months) to MONALEESA-2, potentially due to more favourable baseline disease characteristics.

Pts with HR+, HER2‒ MBC with no prior ET for advanced disease were enrolled...In the advanced setting, 49 pts (17.3%) received RIB+FUL and 222 pts (78.4%) RIB+AI. Prior CT was received by 5 pts (1.8%). In pts evaluable for response, the objective response rate was 31.4%, clinical benefit rate 45.9% and disease control rate 61.1%. Median progression-free survival (mPFS) was 29.7 months in the overall population and 32.7 months in pts with visceral mets. The 12-month OS rate was 90.3%...In RW setting, RIB+ET shows tolerable safety and a mPFS for 1L pts that is in line with MONALEESA trials.

A total of 839 patients received a documented second-line therapy after progression on first-line CDK4/6i treatment....Continuation of the CDK4/6i was associated with improved rwPFS (HR 0.48, 95% CI 0.43-0.53, P < .0001) and OS (HR 0.30, 95% CI 0.26-0.35, P < .0001) compared to chemotherapy....While prospective data are needed, analysis of real-world data suggests a survival benefit for continuation of a CDK4/6i beyond frontline progression for patients with HR+/Her2- MBC.

An unanchored MAIC of progression-free survival (PFS) and OS in first-line patients with HR+/HER2- ABC treated with RIB+FUL versus PAL+LET was conducted using individual patient data from MONALEESA-3 and aggregated data from PALOMA-1....After weighting, OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32-0.77; p = 0.0020).

...OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32– 0.77; p = 0.0020). PFS favored RIB+FUL versus PAL+LET...OS comparisons favored RIB+FUL over PAL+LET as first-line treatment in postmenopausal patients with HR+/HER2− ABC....PFS and OS for ribociclib plus fulvestrant versus palbociclib plus letrozole based on the MONALEESA-3 and PALOMA-1 trials, demonstrated a significantly longer OS and numerically longer PFS with ribociclib plus fulvestrant.

The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2- BC....subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59-29.61, p < 0.001; palbociclib: OR = 7.39, 95% CI = 1.26-43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41-20.11, p < 0.001).

This was a retrospective, population-based, cohort study of patients with HR-positive, HER2-negative MBC who received a CDK4/6i in combination with an AI as first-line treatment in the metastatic setting.... After a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7–NR)....Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively....CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favourable PFS and early OS outcomes.

Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib...CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes

KARMA is a secondary data use, non-interventional study of Australian patients who received first line treatment with ribociclib and aromatase inhibitor (AI), obtained via a MAP, for HR+, HER2- MBC...Landmark PFS was 76% at 12 months, 67% at 18 months and 64% at 24 months...This real-world cohort achieved a superior PFS.

HR+/HER-2- ABC patients treated with CDK4/6 inhibitors combined with ET had significantly prolonged progression-free survival (PFS) and improved objective response rate (ORR) and clinical benefit rate (CBR)....the patients in experimental intervention groups were treated with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib)...groups treated with CDK4/6 inhibitors (palbociclib, ribociclib or abemaciclib) combined with ET had a prolonged PFS compared with the endocrine monotherapy groups (HR = 0.55, 95% CI: 0.50–0.60, p < 0.001...

A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken....In this retrospective exploratory analysis of hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer, each intrinsic subtype exhibited a consistent PFS benefit with RIB, except for basal-like.

This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR+/HER2− BC….Recommended phase II doses (all once daily days 1-28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% CI, 31.1%-51.6%), which met the primary endpoint (predetermined threshold: 10%).

Using an MAIC to adjust for trial differences revealed PFS and OS results favoring 1L RIB+ FUL vs. PAL+LET in postmenopausal pts with HR+/HER2− ABC, and demonstrated a significant benefit for OS.

Turkish MAP enabled access to ribociclib in combination with letrozole as first-line therapy for MBC patients with HR positive and Her-2 negative tumors….Twelve patients had complete remission as their best response. Median PFS was 24.12 months (95%CI 22.2-26.2).

Patients (pts) with HR+, HER2– ABC, ≤ 1 line of prior CT and no prior ET for ABC received RIB+LET…Median time to progression was 27.1 mos (95% CI, 25.7-NE), overall response rate was 43.6% (95% CI, 41.5-45.8%), and clinical benefit rate was 69.1% (95% CI, 67.1-71.1%) for pts with measurable disease at baseline....This analysis confirms the safety and efficacy of RIB+LET in a large, diverse cohort of pts with HR+, HER2– ABC (with no previous ET for ABC), closely resembling real-world clinical practice.

Adding abemaciclib/palbociclib/ribociclib to AI (HR: 0.55, 95% CI 0.48-0.64) or abemaciclib/palbociclib to fulvestrant (HR: 0.49, 95% CI 0.37-0.63) improved significantly the PFS of metastatic HR+ Her 2- breast cancers regardless menopausal status and site of metastasis.

Also, in pretreated HR+/HER2- advanced breast cancer (ABC) patients, after combination of Ribociclib plus Fulvestrant therapy, partial responses (PRs) were observed in patients with prior treatment of Fulvestrant.

Herein, we presented a patient with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer who demonstrated a complete metabolic response on 18F-FDG PET/CT to treatment with a CDK4/6 inhibitor (ribociclib).