Ibrance is indicated for the treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer:...in combination with an aromatase inhibitor…in combination with fulvestrant in women who have received prior endocrine therapy.

IBRANCE is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with...an aromatase inhibitor as initial endocrine-based therapy...fulvestrant in patients who have received prior therapy

IBRANCE 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 breast cancer in combination with:..an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men...or...fulvestrant in patients with disease progression following endocrine therapy.

FASLODEX is an estrogen receptor antagonist indicated for the treatment of:...HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy.

Palbociclib (also called Ibrance and made by Pfizer) given with fulvestrant, another type of anti-cancer treatment, is recommended for adults with a type of advanced breast cancer called hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have already had hormone therapy.

Comparison across multiple trials, including those in the second-line settings studying combination of fulvestrant with palbociclib or abemaciclib have shown statistically significant improvement in PFS. Based on the results of the Monaleesa-3 trial and extrapolation results from the second-line setting, the NCCN Panel has included fulvestrant in combination with CDK 4/6 inhibitors as a category 1 first-line option for postmenopausal women and premenopausal women with ovarian ablation/suppression with HR-positive, HER2-negative recurrent/stage IV breast cancer.

Median PFS was 24.4 months (95% CI: 13.1, 32.4) with P + TAM and 11.1 months (95% CI: 7.4, 14.6) with placebo + TAM (hazard ratio [HR]: 0.602 [95% CI: 0.428, 0.848], 1-sided p-value from stratified log rank test: 0.002)….The study achieved its primary endpoint, demonstrating a significant and clinically meaningful improvement in PFS for P + TAM compared with placebo + TAM for pts with HR+/HER2− ABC. Early OS data with P+TAM is encouraging.

Across all subgroups analyzed, the median progression-free survival (PFS) was longer in the PAL plus ET arm than the PBO plus ET arm. TTC was longer with PAL plus ET versus PBO plus ET across the same patient subgroups in both studies....Taken together, these findings in combination with the current body of literature regarding PFS and TTC benefits with CDK4/6 inhibitors suggest that patients receive greater clinical benefit from palbociclib plus ET compared with ET monotherapy for the treatment of HR+/HER2− ABC.

After a median follow-up 37.9 mo, median rwPFS (95% CI) was 32.2 mo (29.4–35.1) and 24.2 mo (19.9–30.1) in the 1L and ≥2L settings, respectively….After a median follow-up of 35.7 mo, median OS (95% CI) was 50.8 mo (42.3–65.4) and 40.0 mo (32.2–43.1) in the 1L and ≥2L settings, respectively....Results from this large prospective, real-world study are consistent with clinical trial results and support the use of PAL + ET for the treatment of HR+/HER2– ABC.

The median OS [95% confidence interval (CI)] was 34.8 months (28.8-39.9) in the palbociclib group and 28.0 months (23.5-33.8) in the placebo group (stratified hazard ratio, 0.81; 95% CI, 0.65-0.99). The 6-year OS rate (95% CI) was 19.1% (14.9-23.7) and 12.9% (8.0-19.1) in the palbociclib and placebo groups, respectively....The clinically meaningful improvement in OS associated with palbociclib plus fulvestrant was maintained with >6 years of follow-up in patients with HR+/HER2- ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients.

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.

At 12 months, PFR for palbociclib + AI was 88.1%, and SR was 97.3%; PFR for palbociclib + fulvestrant was 79.8%, and SR was 97.5%....Low dose-reduction rates and favorable PFRs and SRs suggest that palbociclib + AI/fulvestrant is well tolerated and effective for HR+/HER2– ABC/MBC in real-world clinical practice.

PAL + FUL was associated with more favorable patient-reported outcomes than ABEM + FUL in patients with HR+/HER2- advanced breast cancer.

…phase III open-label trial in which pts with stage II-III HR+/HER2- eBC were randomized to receive either 2 years of P with adjuvant ET (P+ET) or ET alone…this analysis of the PALLAS trial shows that the addition of 2 years of P to ongoing adjuvant ET did not improve survival endpoints for pts with stage II-III HR+/HER2- eBC.

...PALOMA-3 trial support the sustained and clinically meaningful survival benefits of palbociclib added to fulvestrant across a range of patients with HR-positive, HER2-negative advanced breast cancer...

The clinically meaningful improvement in OS with PAL+FUL was maintained with >6 years of median follow-up in pts with HR+/HER2– ABC who had progressed on prior endocrine treatment. 

In this “real-world” population of patients with HR+/HER2− MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant...Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2- ABC, regardless of menopausal status.

NON-SUPPORTIVE EVIDENCE: 3-year invasive disease-free survival was 88·2% (95% CI 85·2–90·6) for palbociclib plus endocrine therapy and 88·5% (85·8–90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76–1·15]; log-rank p=0·51)...adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting.

Median PFS was prolonged with palbociclib plus letrozole compared with placebo plus letrozole in patients....Among patients who provided metastatic disease tumor tissues, palbociclib plus fulvestrant improved PFS compared with placebo plus fulvestrant...These findings support palbociclib plus endocrine therapy as standard of care for HR+/HER2- ABC patients...

This retrospective medical chart review study included postmenopausal women with confirmed HR-positive/HER2-negative ABC or MBC...The 6-month progression-free survival rate was 94% for patients treated with palbociclib plus letrozole and 95% for patients treated with palbociclib plus fulvestrant; 85% and 80% of patients treated with palbociclib plus letrozole were progression free at 12 and 18 months, respectively.

In HR+/HER2– ABC pts, PAL+FUL showed a clinically meaningful improvement in OS (6.9 mo vs PBO+FUL), especially in pts with sensitivity to prior ET. The absolute difference of PFS gain was maintained in OS.

...female patients in the US with HR+/HER2- ABC/MBC who received palbociclib + fulvestrant...Palbociclib + fulvestrant appears to be effective and well tolerated in first line ABC/ MBC settings in women who have previously failed endocrine therapy.

In the PALOMA-3 trial (NCT01942135), 108 of 521 patients were premenopausal, were treated with palbociclib (or placebo) + fulvestrant + goserelin, and had prior therapy for ABC (75%) or early (25%). Median PFS in premenopausal patients with palbociclib (n = 72) vs placebo (n = 36) was 9.5 vs 5.6 months...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.

...To compare invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC)...

...To compare invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC)...

Median CFS was 69.1 months (95% CI, 24.2–85.4), and that was longer in patients with nonvisceral versus visceral metastases (77.5 vs 37.5 months). At the data cutoff, 3 patients (7.1%) were still receiving PAL plus LET (90.9–93.2 months)….This interim analysis showed a median OS of >7 years with 1L PAL plus LET.

In this multicenter, observational study, patients with HR+/HER2- ABC, who initiated PAL + ET...Our real-world data are consistent with findings form the PALOMA-2 and PALOMA-3 studies and those from RWE in routine United States clinical practice. FUL was the most commonly endocrine partner with PAL regardless of treatment lines. These observations add to the body of evidence supporting PAL effectiveness in clinical practice for Japanese ABC patients.

The Phase 2 PARSIFAL study assessed whether fulvestrant (FUL) or letrozole (LET) was the optimal endocrine partner for the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib (PAL) in patients (pts) with untreated, endocrine-sensitive, hormone receptor positive (HR+)/HER2-negative (HER2-) advanced breast cancer (ABC)...A total of 86 pts (22.1% of the population) had a mPFS time <12 mo (early progressors). mOS and mPFS for this early progressor subgroup were 24.0 mo (95%CI, 17.3-30.1) and 7.0 mo (95%CI, 5.6-8.3), respectively, and only 11 pts (12.8%) were still alive at the time of analysis.

Overall, palbociclib was used in 44% and ribociclib in 26% of all first-line treatments in OPAL….IPTW-adjusted median OS was 36.7 months (95%-CI 33.0 – NA) for the palbociclib and 36.6 months (95%-CI 33.1 – NA) for the ribociclib group….This analysis of real word data in the OPAL registry platform showed similar PFS and OS for palbociclib + ET compared to ribociclib + ET...

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.

We compared overall survival (OS) and real-world progression-free survival (rwPFS) of palbociclib plus AI (PAL+AI) vs AI alone in HR+/HER2􀀀 MBC patients with CVDFirst-line PAL in combination with AI is associated with prolonged OS and rwPFS in patients with HR+/HER2􀀀 MBC and CVD in a real-world setting compared with AI alone.

In the real-world population of patients, palbociclib combined with AI endocrine therapy is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy.

PAL + AI versus AI alone was associated with significantly prolonged OS (HR = 0.62; p < 0.001) and rwPFS (HR = 0.55; p < 0.001) in patients with lung metastases and numerically longer OS (HR = 0.73; p = 0.056) and significantly longer rwPFS (HR = 0.57, p < 0.001) for those with liver metastases. Overall, PAL + AI versus AI alone was associated with prolonged OS and rwPFS in routine clinical practice, supporting the use of first-line PAL + AI for patients with HR+/HER2- mBC with lung and/or liver metastases.

One patient (6.7%) achieved a complete tumor response, 4 (26.7%) a partial response, and 8 (53.3%) stable disease. Median rwPFS was 19.8 months (95% CI, 7.4–38.0). Median follow-up duration was 24.7 months (95% CI, 20.0–35.7)….This real-world analysis showed that palbociclib was well tolerated and provides preliminary data on treatment patterns and outcomes with palbociclib in male patients with HR+/HER2– ABC, helping inform the use of palbociclib in this patient subgroup.

POLARIS is a prospective observational study of pts with HR+/HER2− ABC receiving palbociclib in clinical practice in the US and Canada....Pts with HR+/HER2− ABC receiving palbociclib and CCI scores 0 and 1–2 had similar rwPFS and OS regardless of LOT. Pts with CCI score 3+ had shorter rwPFS and OS in the 1LOT, and similar rwPFS but shorter OS in the ≥ 2LOT than pts with score 0–2….

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.

The prospective, non-interventional PERFORM study is going to enroll 1,900 pts from 320 sites across Germany and Austria to gain further insights on effectiveness, tolerability, patient-reported outcomes (PRO) and longitudinal treatment patterns after 1L treatment with palbociclib + ET....Progression-free survival (PFS) rate at 12 months was 71.7%; overall response rate (ORR) and clinical benefit rate (CBR) were 33.2% and 57.4%, respectively....The IA 2 of PERFORM shows comparable results regarding PFS, ORR and CBR of 1L treatment with palbociclib + ET in pts ≥ and <75 years, even though pts ≥75 years required dose modifications more frequently.

In this prospective study we included women with HR+/HER2- MBC progressing to ET plus palbociclib (P)....In the whole population mPFS1 was 17.5 months; mPFS2 was 5 months in the overall cohort (95% CI = 4-48 months) with a significant difference between ET and CT (10 months vs 5 months, p=0.035); CBR was 50% and 55.2%, in ET and CT, respectively….In this real life experience, treatments beyond ET plus P failure provided limited but comparable clinical benefit.

After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51–0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59–0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55–0.87]; P = 0.0014)....This real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2− mBC aged ≥ 75 years.

In this retrospective study, we recruited patients with metastatic HR-positive and HER2-negative breast cancer….We recruited 150 patients who received first-line palbociclib with hormonal therapy....The median progression-free survival (PFS) of the study group was 22 months….

The ORR was 24.8% (95% confidence interval 17.6‒33.2), and the median duration of treatment was 10.6 months (range 0.1‒29.3)….Palbociclib in combination with letrozole was generally well tolerated with a clinically manageable safety profile; the observed ORR supported treatment benefit in Latin American women with HR+/HER2− ABC.

This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer...initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone...OS rates were higher for patients treated with palbociclib plus an AI than for those treated with an AI alone at 12 months (91.7% vs. 70.3%, respectively), 24 months (75.9% vs. 53.2%), and 36 months (61.2% vs. 44.3%)...This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings.

Real-world response rates (complete or partial response) were 52.1% and 46.2%, respectively (odds ratio, 1.27 [95% confidence interval 0.72‒2.24]). Among patients with one or more tumor assessments on treatment, real-world response rates were 60.0% in the palbociclib plus AI cohort (n = 103) and 49.9% in the AI cohort (n = 71; odds ratio, 1.51 [95% confidence interval 0.82‒2.77])....This real-world analysis suggests that pre/perimenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer appear more likely to respond to palbociclib plus AI versus AI alone as first-line therapy...

This research retrospectively analyzed the efficacy and safety of Palbociclib combined with ET in 214 patients with HR+/HER2- MBC….Median PFS was 7.17 months (95% CI: 7.61–10.05 months), with an objective response rate (ORR) of 2.80% and a disease control rate (DCR) of 34.58%.

The median OS2 was 42.3 months with capecitabine, 35.7 months with fulvestrant, 30.7 months with exemestane and everolimus, and 23.1 months with cytotoxic chemotherapy....This up-to-date survival analysis found that first-line treatment of HR+HER2− MBC patients with palbociclib and letrozole provided a median PFS of 29.0 months….In addition, the five-year OS rate was 66.5%.

The efficacy of palbociclib plus AI is worthy of recognition and the toxicity was acceptable. Compared with fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy, Palbociclib plus AI...have a better survival.

In the balanced subgroup analysis, TTF showed a similar trend to that in the overall population, and in patients with de-novo metastatic disease and non-central nervous system (CNS) metastasis, OS was significantly longer in the PAL plus ET group than ET (HR=0.256, 95% CI: 0.112-0.586, p for interaction =0.013; HR=0.657, 95% CI: 0.443-0.973, p for interaction=0.013, respectively)...Comparatively, PAL plus ET had significantly longer TTF than ET, supporting the use of PAL plus ET in HR+/HER2– ABC patients in real-world settings. In patients with de-novo metastatic disease and non-CNS metastasis, PAL plus ET showed significant OS benefit...

For all 891 patients with lung or liver metastases, OS and rwPFS were significantly prolonged in the Pal + AI group versus AI alone group following sIPTW (HR = 0.64; P<0.001 and 0.57; P<0.001, respectively)...Pal + AI versus an AI alone demonstrated prolonged OS and rwPFS in routine practice, supporting the use of 1L Pal + AI for patients with HR+/HER2− mBC with visceral metastatic diseases.

Before surgery (SUR), patients received palbociclib 125mg for 21 days and letrozole until SUR....In chemo-resistant residual disease in pts with HR+/HER2- BC, palbociclib induce a potent anti-proliferative effect. A direct relationship between immune infiltration and anti-proliferative response exists, where immune infiltration is increased in residual tumors with CCCA.

The median PFS in group B (combination therapy) was 9.4 (90% confidence interval [CI]: 6.9-11.2) months (p < 0.001)….Our findings suggest that palbociclib plus fulvestrant after disease progression despite fulvestrant monotherapy is potentially safe and effective in patients with HR-positive/HER2-negative advanced MBC.

HR+/HER2- MBC patients who received Palbociclib...46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%....Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 - MBC.

...women with confirmed hormone receptor-positive, HER2-negative advanced/metastatic breast cancer treated with palbociclib plus an AI or with palbociclib plus fulvestrant...The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both groups. The objective response rates were 80% for palbociclib plus an AI and 75% for palbociclib plus fulvestrant.

This comparative analysis of palbociclib plus AI vs AI alone provides evidence that first-line palbociclib in combination with endocrine is associated with improved effectiveness for AA patients with HR+/HER2- MBC in the real-world setting.

Palbociclib combined with AI or fulvestrant had a median PFS of 34 months (95% confidence interval [CI] = 6.87-61.13) and 12 months (95%CI = 7.76-16.24), respectively....Palbociclib combined with endocrine therapy has a favorable efficacy and acceptable toxicity in HR+/HER2- Chinese MBC patients.

After stabilized inverse probability treatment weighting, median OS (95% CI) is significantly longer among palbociclib versus AI recipients (49.1 [45.2-57.7] versus 43.2 [37.6-48.0] months; hazard ratio, 0.76 [95% CI, 0.65-0.87]; P < 0.0001). Progression-free survival (95% CI) is 19.3 (17.5-20.7) versus 13.9 (12.5-15.2) months, respectively (hazard ratio, 0.70 [95% CI, 0.62-0.78]; P < 0.0001). These data support first-line palbociclib plus an AI treatment for HR+/HER2- MBC.

We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2- advanced breast cancer who progressed on prior ET...The study met its primary endpoint, with a clinical benefit rate of 33.3%...The median progression free survival (PFS) was 3.6 months (CI95% 2.0-7.2)....The combination of palbocilib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pre-treated patient population with advanced HR+/HER2- breast cancer.

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.

...palbociclib-based regimen in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC)….Among 33 patients enrolled, CBR was 34.4% (95%CI, 18.6-53.2; P<0.001)...Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients.

Median PFS of the study treatment in patients with resistance to fulvestrant monotherapy was 9.4 months (90% Confidence interval 6.9- 11.2 months, p<0.001)….Our data suggest that palbociclib plus fulvestrant beyond disease progression to fulvestrant monotherapy is possibly effective and safe in patients with HR-positive HER2-negative ABC/MBC.

In this real-world analysis, the majority of patients received palbociclib as the CDK4/6 inhibitor with letrozole or fulvestrant as the predominant endocrine therapies. The median progression-free survival (PFS) in the letrozole (27.6 months) and fulvestrant (17.2 months) groups were comparable to that observed in clinical trials....The real-world progression-free survival with CDK4/6 inhibitors mimics that observed in the clinical trial.

The median follow‑up time was 31.0 months [95% confidence interval (CI), 16.9‑44.9] and the median PFS time was 16.3 months (95% CI, 11.4‑21.2), with 58% of patients remaining progression‑free at 12 months....Overall, real‑world data showed that administration of palbociclib in combination with ET in patients with advanced HR+ breast cancer achieved a favorable outcome that was comparable to that reported in clinical trials.

With a median follow-up period of 22.4 months, the median progression-free survival (mPFS) was 12.3 months, the median time to failure (mTTF) was 11.8 months, and the median overall survival (mOS) was 35.5 months. Moreover, the 1-year PFS, TTF and OS rates were 50.8%, 49.0% and 87.6%, respectively. Of the 155 with measurable disease, the objective response rate (ORR) was 27.1%, the disease control rate (DCR) was 71.6% and the clinical benefit rate (CBR) was 81.3%....Treatment with Palbociclib plus ET exhibited favorable efficacy for HR+HER2– ABC in Chinese real-world practices, especially for non-liver, non-CNS metastasis or premenopausal patients. Early-line treatment yielded more durable benefits, and response to CR/PR indicated a better PFS prognosis.

The present single-arm study evaluates the real world experience of efficacy and safety of Palbociclib-Letrozole for the treatment of HR+/HER2- MBC in the Indian population….About 17% (23/100) patients achieved an objective response, while 54% (57/100) showed disease control....In the present study, Palbociclib + Letrozole reported good clinical response at the end of treatment duration with a manageable tolerability profile in the Indian population.

IRIS was a retrospective chart review study of patients with confirmed HR+/HER2- ABC/MBC receiving palbociclib according to approved indications in real-world clinical practice....Most patients were initiated on palbociclib 125 mg/d (P+AI, 63.2%; P+F, 78.3%). PFRs at 12 and 24 months were 76.2% and 52.6%, respectively, for P+AI and 71.6% and 65.6%, respectively for P+F....In this analysis of the Japanese IRIS cohort, outcomes in terms of PFRs and SRs appear to be better with first- versus second or later-line palbociclib, regardless of the endocrine partner.

We conducted a retrospective analysis of HR+/HER2– MBC patients….Median OS in PB+AI vs AI was 53.4 (95%CI=48.7-58.6) vs 40.4 (95%CI=36.3-44.9) months (mo) (HR=0.67, 95%CI=0.60-0.76, p<.0001), respectively. After sIPTW, median OS was 49.1 mo (95%CI=45.2-57.7) for PB+AI vs 43.2 mo (95%CI=37.6-48.0) for AI (HR=0.76, 95%CI=0.65-0.87, p<.0001). After 1:1 PSM, median OS was 57.8 mo (95%CI=47.2-NR) with matched PB+AI vs 43.5 mo (95%CI=37.6-48.9) with matched AI (HR=0.72, 95%CI=0.62-0.83, p<.0001)....This largest to date real-world comparative effectiveness study demonstrated that palbociclib +AI was significantly associated with prolonged overall survival vs AI alone, supporting first-line palbociclib plus AI as a standard of care for HR+/HER2– MBC patients.

The clinical benefit rate was 66.66%, the median PFS had not been achieved after 12 months being Hazard Ratio 0.69 (95% CI 0.58-0.82); 68.11 % of patients have not progressed….Colombian patients diagnosed with HR+/HER2- advanced or metastatic breast cancer treated with palbociclib in combination with fulvestrant as second or later lines of treatment was found to be effective treatment in terms of PFS and maintained the safety profile observed in the pivotal and observational studies.

Eligible patients were females with HR+ and Her2- advanced breast cancer, receiving Palbociclib in combination with Letrozole....PFS recorded a median of 19.07 months (95% CI=15.43-22.71). PFS had a median of 12.99 months in the absence of progesterone receptors (vs 20.05 months in the case of positive estrogen and progesterone receptors; P = 0.046), a median of 13.02 months in the presence of liver metastases (vs 22.98 months in the absence of liver metastases; P = 0.007), and 15.94 months in the case of second-line and beyond (vs 22.98 months in the case of first-line; P = 0.033)....

We conducted a retrospective, observational chart review of all female patients at our clinics with HR+, HER2- metastatic breast cancer receiving palbociclib in combination with either letrozole or fulvestrant...The median PFS for all clinic patients receiving palbociclib and letrozole (n = 63) was 40.8 months (95% confidence interval (CI) 25.6-not estimable) and 16.97 months (95% CI 8.57-not estimable) for patients receiving palbociclib and fulvestrant (n = 11)....We conclude that alternative dosing strategies used by oncologists such as prescribing palbociclib for three weeks on, two weeks off may achieve comparable disease control...

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor...The median (95% CI) real-world progression-free survival was 31.7 (27.9-not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%....These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2- A/MBC.

...in the second-line setting, with 380 propensity-matched-cohort, the palbociclib group had significantly longer PFS (10 vs 5 months, p<0.0001) as well as OS (33 vs 24 months; p < 0.022), compared to controls. We conclude that in this single center analysis of a large cohort of metastatic HR+ HER2- BC patients, palbociclib in combination with ET was associated with improved PFS in both first- and second-line settings and OS in the second-line setting compared with ET alone cohort.

For all patients treated with palbociclib, median progression-free survival by the end of the study period was 14.4 months (95% confidence interval [CI] 6.2-22.2 months)....This study provides data from a real-world setting that match the results of previous studies in terms of effectiveness (i.e., progression-free survival) when palbociclib plus endocrine therapy was used as second- or third-line treatment.

Among these patients, 88 patients received palbociclib combined with ET as first-line therapy, and achieved a median progression-free survival (mPFS) of 19.8 months and an objective response rate (ORR) of 40.9%, meanwhile, in the first-line setting, 62 patients received palbociclib at an initial dose of 125 mg, achieving a mPFS of 20.9 months and an ORR of 46.8%....Palbociclib combined with ET is an effective therapeutic regimen for HR+/HER2- ABC, particularly in the first-line setting with palbociclib initial dose of 125 mg, and AEs were manageable.

The objective response rate was 19.4% (95% CI, 14.7%-24.9%) overall and 2.3% in Australian patients with ≥2 lines of prior therapy for metastatic disease…. In an expanded access setting in Australia and India, palbociclib plus letrozole was well tolerated in patients with HR+/HER2- ABC...

PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36–0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37–0.64, P = 0.001)....Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients.

The ORR was 48.8%, and DCR was 88.4%. The median PFS was 12.0 months (95%CI, 11.1-13.0 months), and the median TTF was 8.50 months (95%CI, 2.5-14.5 months)….Palbociclib combined with endocrine therapy in patients with HR+/HER2-advanced breast cancer has good efficacy and controllable adverse reactions.

At 12 months, PFR for palbociclib + AI was 88.1%, and SR was 97.3%; PFR for palbociclib + fulvestrant was 79.8%, and SR was 97.5%.... Low dose-reduction rates and favorable PFRs and SRs suggest that palbociclib + AI/fulvestrant is well tolerated and effective for HR+/HER2- ABC/MBC in real-world clinical practice.

We recruited patients with HR+/HER2- MBC from August 2018 to July 2020 across 7 hospitals in North China.....Palbociclib plus ET significantly prolonged PFS for patients with HR+/HER2- MBC who received first-line therapy, with manageable toxicity.

In Japanese patients, palbociclib was shown to be effective with a manageable safety profile, although differences were observed in the frequency of adverse event and dosing parameters. Current evidence supporting palbociclib as a first-line treatment strategy for patients with HR+/HER2‒ ABC in Asia, and specifically japan...

Median rwPFS was 15.4 months (95%CI = 12.5 - 19.5) in PB+LE patients and 10.2 months (95%CI=8.0-11.7) in LE patients (HR=0.60, 95%CI=0.49-0.74, p <0.0001; Adjusted HR=0.56, 95%CI=0.45-0.71, p <0.0001). This real-world comparative analysis provides evidence that palbociclib in combination with letrozole is associated with improved outcomes compared to letrozole alone for HR+/HER2- MBC patients with lung or liver metastases in the first-line setting.

This post hoc analysis describes the efficacy and safety of PAL + ET in Black and Hispanic patients with HR+/HER2- ABC enrolled in the PALOMA trials. PAL+ ET prolonged median PFS in PALOMA-2 and -3 and prolonged median OS in PALOMA-3 compared to PBO + ET.

We aimed to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment in HR-positive/HER2-negative EBC pts with an Oncotype DX RS ≥18....Participants were pre- and post-menopausal women aged ≥18 years with centrally confirmed HRpositive/HER2-negative…. a significant proportion of HR-positive/HER2-negative EBC pts with high RS at baseline achieve a pathological or molecular downstaging with this regimen.

In this single center analysis, of a large cohort of metastatic HR+ HER2- BCpatients, palbociclib in combination with endocrine therapy was associated with improved PFS…

POLARIS is a prospective, noninterventional real-world study of patients with HR+/HER2- ABC who received palbociclib...Among patients who received palbociclib in the first line setting (n=9), 1 had a CR and 3 had a PR...

Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor–positive, ERBB2-negative advanced breast cancer.

This retrospective study aimed to explore the clinical efficacy of palbociclib with endocrine therapy (ET) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer in real-world practice....The median PFS was 12.8 months (95% confidence interval: 10.1-15.5)....The overall response rate was 10.1%, and the clinical benefit rate was 78.3%....ET combined with palbociclib treatment was effective and well-tolerated in HR+/HER2- metastatic breast cancer patients in the real-world setting.

The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial

Between February 2015 and February 2019, 796 HR+/HER2– MBC women aged ≥ 65 years started PB+LE or LE as first-line therapy….Median rwPFS was 22.2 months (95%CI = 20.0-30.4) in PB+LE cohort and 15.8 months (95%CI=12.9-18.9) in LE cohort (HR=0.59, 95%CI=0.47-0.74, p <.0001). Median OS was not reached (NR) in PB+LE cohort vs 43.4 months (95%CI=30.0—NR) in LE cohort (HR=0.55, 95%CI=0.42-0.72, p <.0001).

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).

The rwBTR rate (complete response+partial response) in the first-line setting was 59.8% in the PAL+LET group and 39.2% in the LET group (odds ratio 2.31 (95% CI 1.75‒3.04), P < 0.0001). After 1:1 propensity-score matching, the rwBTR rate was 58.6% in the PAL+LET group versus 39.1% in the LET group (odds ratio 2.21 (95% CI 1.50‒3.25), P < 0.0001). HR+/HER2‒ MBC patients were more likely to respond to PAL+LET compared to LET.

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.

Exploratory analyses suggest improved OS with palbociclib-fulvestrant versus placebo-fulvestrant in patients with no prior chemotherapy for ABC...overall survival in HR+/HER2- ABC include the absence of prior chemotherapy in the advanced setting...

...an open-label, single-arm, multicenter phase II trial of palbociclib in combination with tamoxifen in patients with HR+/HER2 - advanced BC...Best response per RECIST1.1: 14 pts (34%) had PR, 18 pts (44%) had SD…

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.

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...

IBRANCE® (palbociclib) in combination with letrozole was associated with improved real-world progression-free survival (rwPFS) and overall survival (OS) in women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (mBC) compared with letrozole alone.

In this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.

Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively….Our data indicate that palbociclib plus ET is active and safe in HR+/HER2- MBC, also suggesting a better performance of the combinations in earlier treatment lines.

This retrospective chart review included women with HR+/HER2- ABC/MBC receiving P+L or P+F in Canada….The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%....Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.

In total, 130 patients were included in the study, of whom 87.0% of patients started palbociclib on 125 mg/day,...After a median follow-up period of 10.6 months, the median progression-free survival was 9.2 months....The findings from this real-world single-center study in China showed that treatment with palbociclib plus ET exhibited favorable efficacy and good tolerance in patients with HR+ and HER2- MBC, even in patients who were initially resistant to endocrine therapy, and there was no difference in outcomes between subsequent treatment with chemotherapy and ET.

Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25mg/day for 28-days, palbociclib 125mg/day for 21-days, plus leuprolide 3.75mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250mg/m² twice daily for 14 days every 3 weeks)....palbociclib+ET prolonged mPFS compared with capecitabine in tamoxifen-sensitive (20.5 vs. 12.6 months) and tamoxifen-resistant (20.1 vs. 14.5 months) patients....This post post-hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2- MBC patients irrespective of tamoxifen sensitivity.

...patients with HR+ HER2- ABC treated with a palbociclib-based therapy as 1st or 2nd line of therapy...Palbociclib was prescribed in the 1st line setting for 72.6% of pts and in the 2nd line setting for 27.4% of pts. The initial dose was 125 mg daily (95.2%). It was associated with an aromatase inhibitor (66.8%) or with fulvestrant (33.2%)...At 12 m from the initiation of palbociclib, 94.5% of the pts were alive. Median progression free survival was 23.4 m (95%CI: 21.6-NR) for pts without previous endocrine therapy, 22.7 m (95%CI: 14.7-NR) for pts who have shown endocrine sensibility, HR=1.2 (95%CI: 0.81-1.77), p=0.0027 and 13.4 m (95%CI: 10.7-20.8) for pts who have not shown endocrine sensibility, HR=1.88 (95%CI: 1.29- 2.73), p=0.003.

...palbociclib (PAL) in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC)...The ORR was 50% (2 CR, 13 PR, 95% CI: 33.15%-66.85%) in 30 pts with measurable disease (n=29)...The median PFS (mPFS) was 24.3 mo (95% CI 15~not reached (NR)) overall.

...PFS rates at 1-year were 83.5% and 71.9% in F/P and F/PL groups, respectively...Overall response rates were 68.3% (F/P) vs. 42.2% (F/PL) (p=0.004)….P/F significantly improved 1-year PFS rate compared to F/PL in pts with HR+/HER2- endocrine sensitive ABC. P/F also improved median PFS and ORR.

This is a multicenter retrospective study of real world experience of patients with HR+, Her 2 neu negative MBC who received Palbociclib in 5 centers of south India between Oct 2016 and Aug 2019….Best response was CR 3 (6%), PR 23 (46%), SD 4 (8%), PD 17 (34%), not assessed 3 (6%). ORR was 52%. The median PFS was 14 months.

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.….The median progression free survival was 262.6 months for palbociclib combined with letrozole as first line.

A simple combined clinical model predicts PFS in HR+/HER2- advanced disease treated with CDK4/6i and ET.

Palbociclib was the first CDK 4/6 inhibitor approved in Germany for HR+/HER2- advanced/metastatic breast cancer (aBC/mBC) in combination with an aromatase inhibitor (P+AI) or fulvestrant (P+F). Palbociclib combination therapy demonstrates effectiveness in terms of progression free and survival rates however follow-up is limited at this time.

...Of the 162 patients, 105 (64.8%) received palbociclib + letrozole and 57 (35.2%) received palbociclib + fulvestrant. The 6 month progression free rate for palbociclib + letrozole was 94.3% and for palbociclib + fulvestrant was 95.0%. At 12 months, progression free rate for palbociclib + letrozole was 85.4%. The survival rate at 6 and 12 months for palbociclib + letrozole was 98.1% and 93.4% respectively and the survival rate at 6 months for palbociclib + fulvestrant was 98.2%...palbociclib combined with letrozole or fulvestrant demonstrates high effectiveness in terms of progression free and survival rates.

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.

During a median follow-up of 17 months (IQR 9-22), median progression-free survival was 20·1 months (95% CI 14·2-21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1-17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], one-sided log-rank p=0·0235)....Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Herein, we describe the case of a 54- year-old woman with advanced breast cancer, which showed receptor conversion from primary tumor(triple-negative)to distant metastases(Luminal type)....Furthermore, immunohistochemistry results showed that the metastatic tumor was ER-positive, PgR-positive, and HER2-negative. Fulvestrant and palbociclib were then initiated as first-line endocrine therapy. She has been stable for more than 18 months since.

Herein, we report the clinical history of a young woman with HR-positive HER2-negative metastatic BC and a pancytopenia due to carcinomatosis of the bone marrow receiving letrozole and leuprorelin plus the CDK4/6 inhibitor palbociclib, who significantly derived clinical benefit from treatment.