Impact of Body Mass Index And Its Change on Survival Outcomes In Patients With Early Breast Cancer: A Pooled Analysis Of Individual-Level Data From BCIRG-001 and BCIRG-005 Trials

Background

The relationships between body mass index (BMI) and survival outcomes are complex and have not been thoroughly investigated in breast cancer patients who received adjuvant chemotherapy.

Aim

The objective was to examine the effect of baseline BMI, BMI after adjuvant chemotherapy, and BMI change from baseline to post-adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS).

Methods

We collected data on 2394 patients from two randomized, phase III clinical trials that investigated adjuvant chemotherapy in breast cancer identified in Project Data Sphere. Restricted cubic splines, adjusting for confounding factors, were used to examine potential non-linear associations between continuous BMI value and survival. Stratified analyses involved chemotherapy regimens used.

Results

• On multivariate analysis, severe obesity (BMI≥40.0 kg/m²) at baseline was independently associated with worse DFS (HR=1.48, 95%CI 1.02-2.16, P=0.04) and OS (HR=1.79, 95%CI 1.17-2.74, P=0.007) compared with underweight/normal weight (BMI≤24.9 kg/m²).
• A BMI loss >10% was also an independent prognostic factor for adverse OS (HR=2.14, 95%CI 1.17-3.93, P=0.014).
• When stratified by chemotherapy regimens, the multivariate analysis revealed that severe obesity adversely affected DFS (HR=2.38, 95%CI 1.26-4.34, P=0.007) and OS (HR=2.90, 95%CI 1.46-5.76, P=0.002) in the docetaxel-based group, but not in the non-docetaxel-based group.
• Restricted cubic splines revealed a “J-shaped” association of baseline BMI with risk of recurrence (P for non-linearity=0.111) or all-cause death (P for non-linearity=0.008), and this relationship was more pronounced in the docetaxel-based group (DFS: P for non-linearity=0.011; OS: P for non-linearity <0.001).

Conclusion

• In early breast cancer patients treated with adjuvant chemotherapy, baseline severe obesity was lined to worse DFS and OS, while a BMI loss over 10% from baseline to post-adjuvant chemotherapy also negatively affected OS.
• Moreover, the prognostic role of BMI might differ between docetaxel-based and non-docetaxel-based groups.

Reference

Annals of Oncology (2023) 34 (suppl_2): S278-S324. 10.1016/annonc/annonc1297

 

Prognostic and Predictive Impact of Estrogen/Progesterone Receptor (ER/PR), and Ki-67 Expression: An Exploratory Analysis From The Monarche Trial In Patients With High-Risk, HR+, HER2-, Early Breast Cancer (EBC)

Background

• The monarchE trial demonstrated that the addition of abemaciclib to endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival in node-positive, high-risk EBC patients (pts) with benefit deepening beyond the 2-year (yr) treatment (tx) period. Ki-67 ≥20% was prognostic of breast cancer outcomes but not predictive of abemaciclib benefit.

  Aim

  Here, the aim was to evaluate expression of ER, PR and Ki-67 to determine their prognostic and predictive impact, including analyses as continuous variables

  Methods

  ER/PR and Ki-67 expression was determined by immunohistochemistry (IHC). The graphical Subpopulation (subp) Tx Effect Pattern Plot (STEPP) analysis was conducted for each biomarker to robustly assess the tx effect ensuring a balance between subp sample size and enough number of overlapping subp. Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ER/PR status subtypes (positive ≥1%).

  Results

• Each IHC cohort varied slightly in number of pts and the precise IDFS HR point estimate (abemacilib+ET vs ET), but STEPP analysis revealed consistent abemaciclib tx benefit regardless of ER, PR or Ki-67 expression.
• The IDFS benefit of abemaciclib was also consistent in ER+/PR+ and ER+/PR- tumors.
• The 3-yr IDFS rates of the control arm showed that pts with PR- tumors had a higher risk of recurrence. Pts with ER- tumors followed a similar trend, but the effect could not be robustly estimated due to small numbers. 

Conclusion

Consistent IDFS benefit of adjuvant abemaciclib was observed regardless of the level of ER, PR or Ki-67 expression, as well as in ER+/PR+ and ER+/PR- tumors. Similar to Ki-67 ≥20%, PR- status was prognostic of worse outcomes with ET alone.

Reference

Annals of Oncology (2023) 34 (suppl_2): S278-S324. 10.1016/annonc/annonc1297

Omission of Breast Surgery After Neoadjuvant Systemic Therapy for Invasive Cancer: Three-Year Preplanned Primary-Endpoint on A Phase II Multicentre Prospective Trial

Background

• Neoadjuvant systemic therapy (NST) for triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2+BC) yields a pathol-ogic complete response (pCR) in approximately 60% of patients.
• A pCR to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB).
• Radiotherapy alone, without breast surgery after NST among patients who had a VACB–determined pCR was evaluated in the feasibility phase (Johnson et al. JACS 2023 ), 2-year pre-planned primary outcome (Kuerer et al Lancet Onc 2022 ), the 32.4 mo patient reported outcomes (Johnson et al SSO 2023 ).

Aim

To report preplanned 3-year primary endpoint.

Method

• This multicentre phase II clinical trial enrolled women aged ≥40 years with unicentric cT1-2N0-1M0 TNBC or HER2+BC and a residual breast lesion <2 cm on imaging after NST.
• One biopsy was obtained by 9G image guided VACB containing a minimum of 12 cores from the tumour bed. If no invasive/in situ disease was identified, breast surgery was omitted, and patients underwent whole-breast radiotherapy/boost.
• Primary outcome was ipsilateral breast tumour recurrence (IBTR) rate and secondary outcomes included evaluation of baseline and longitudinal obtained circulating tumor cells (CTCs) in a total of 33 blood samples and patient-reported outcomes.

Results

• During 2017-2021 50 total patients were enrolled and underwent VACB following NST.
• The mean age was 60·4 years (SD 7·8); 21 patients had TNBC and 29 had HER2+BC.
• Mean imaging final tumour size after NST was 0·90 cm (SD 0·81), and 17 patients (34%) had a complete radiologic response. VACB identified a pCR in 31 patients (62%).
• Among these 31 patients, median follow-up was 38.4 months (IQR: 22.4-49·5) the 3-year IBTR rate was 0% (primary endpoint) and 3-year DFS and OS rates were 100%.
• Two patients were CTC-positive at baseline, 2 were positive at 6-months, and 1 at 12-months. No patients had CTCs detected at more than one timepoint.

Conclusion

Eliminating breast surgery in highly selected patients with an image-guided VACB–determined pCR following NST shows promising 3-year results and additional time and clinical trials evaluating this approach are indicated.

Reference

Annals of Oncology (2023) 34 (suppl_2): S278-S324. 10.1016/annonc/annonc1297

SKB264 (MK-2870) in Previously Treated Hormone Receptor-Positive (HR+)/ HER2-negative Metastatic Breast Cancer (mBC): Results from a Phase I/II, Single-arm, Basket Trial

Background

TROP2 is commonly overexpressed in HR+/HER2- mBC and associated with poor prognosis. SKB264 is a novel anti-TROP2 ADC developed using sulfonyl pyrimidine-CL2A-carbonate linker to conjugate its payload, a belotecan-derivative topoisomerase I inhibitor, to achieve an average Drug-to-antibody Ratio (DAR) of 7.4.

Aim

The objective is to report results from a phase II cohort in patients (pts) with HR+/HER2- mBC.

Methods

• Pts with HR+/HER2- (including HER2-low and HER2-zero) mBC received SKB264 at a dose of 5 mg/kg Q2W until progression or unacceptable toxicity.
• Eligibility included progression on endocrine-based therapy and at least one prior chemotherapy for mBC. Tumor assessment was performed every 8 weeks per RECIST v1.1 assessed by investigator.

Results

• As of data cut-off (April 12, 2023), 41 pts (median age 50 yrs [34-66], 61% ECOG PS 1) were enrolled. Median follow-up was 8.2 months (mo). Treatment-related adverse events (TRAEs) of ≥ Grade 3 were reported in 48.8% (20/41) of pts.
• The most common ≥ Grade 3 TRAEs (≥ 5%) were neutrophil count decreased (36.6%), white blood cell count decreased (22%), anemia (14.6%), platelet count decreased (9.8%) and GGT increase (7.3%). TRAEs led to dose reduction in 17.1% (7/41) of pts.
• No neuropathy or drug related ILD/pneumonitis was reported. No TRAEs led to treatment discontinuation or death. Of 38 pts evaluable for response assessment, 47% of pts had primary endocrine resistance; 79% of pts had received ≥2 prior chemotherapy for metastatic disease, and prior treatments included taxane (100%), and CDK 4/6 inhibitors (65.8%).
• The ORR was 36.8% (14/38, 12 confirmed PR and 2 unconfirmed PR) and DCR was 89.5%, median DoR was 7.4 mo (range, 4.2 to 14.9+), 6-mo DoR rate was 80%. Median PFS was 11.1 mo (95% Cl: 5.4, 13.1), and 6-mo PFS rate was 61.2%.

Conclusion

SKB264 at 5 mg/kg demonstrates a manageable safety profile and promising antitumor activity in pts with pre-treated HR+/HER2- mBC. Two phase 3 studies are currently planned in HR+/HER2- mBC, one in China for pts after at least one chemo for mBC and a second global for pts previously untreated with chemo for mBC, both comparing SKB264 vs investigator selected chemo.

Reference

Annals of Oncology (2023) 34 (suppl_2): S334-S390. 10.1016/annonc/annonc1299

Imlunestrant with or without Everolimus or Alpelisib, in ER+, HER2- advanced Breast Cancer (aBC): Results from the Phase Ia/b EMBER Study

Background

• Imlunestrant is an investigational, next-generation, oral SERD designed to deliver continuous ER target inhibition, including in ESR1-mutant BC.
• In the first-in-human phase 1a/b EMBER study, imlunestrant demonstrated favorable safety, pharmacokinetics (PK), and clinical benefit rate when administered as monotherapy (Jhaveri ASCO 2022) or with abemaciclib (Jhaveri SABCS 2022).

Aim

The objective is to report first clinical data of imlunestrant with everolimus or alpelisib and updated imlunestrant monotherapy data from the EMBER study (NCT04188548).

Methods

• Pts (n = 333) were randomized 1:1 to receive A 840 mg or P q2w + nP 125 mg/m² qw for 6 doses of A followed by A 840 mg or P q2w + doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² q2w for 4 doses of A followed by surgery. 333 pts were assigned to A-chemo (n = 165) or P-chemo (n = 168). Median follow-up was 20.6 mos in the A-chemo arm and 19.8 mos in the P-chemo arm.
• Co-primary endpoints: pCR in ITT or PD-L1+ (PD-L1 IC ≥ 1%) pts. Secondary endpoints: Event-free survival (EFS). Safety was assessed.

Results

• As of 6 Oct 2022, 114 pts received imlunestrant monotherapy, 42 pts received imlunestrant + everolimus, and 21 pts received imlunestrant + alpelisib.
• Baseline characteristics were similar across combination cohorts; 46% pts had visceral disease and 46% had an ESR1 mutation at baseline.
• Median number of prior aBC therapies in combination cohorts was: 1 (range 1-2); including prior ET (100%), CDK4/6i (100%), fulvestrant (35%) and chemo (17%).
• No cardiac or ocular toxicity was seen. Safety and preliminary efficacy are presented.

Conclusion

Imlunestrant alone or in combination with everolimus or alpelisib demonstrated robust efficacy in pts with pre-treated ER+, HER-2 aBC. Toxicities were consistent with the known safety profile of both alpelisib and everolimus.

Reference

Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325.

Datopotamab Deruxtecan (Dato-DXd) Vs Chemotherapy In Previously-Treated Inoperable Or Metastatic Hormone Receptor-Positive, HER2-negative (HR+/HER2–) Breast Cancer (BC): Primary Results From The Randomised Phase III TROPION-Breast01 trial.

Background

• The TROP2-directed antibody-drug conjugate Dato-DXd demonstrated promising activity in heavily pre-treated patients (pts) with inoperable or metastatic HR+/HER2-BC in the Phase 1 TROPION-PanTumor01 trial (NCT03401385).

  Aim

  To report primary PFS results from the global, Phase 3 TROPION-Breast01 trial (NCT05104866).

  Methods

• Adult pts with inoperable or metastatic HR+/HER2-BC, who had experienced progression on endocrine therapy (ET) and for whom ET was unsuitable, and who had received 1-2 prior lines of systemic chemotherapy (CT), were randomised 1:1 to Dato-DXd (6 mg/kg Q3W) or investigator’s choice of CT (ICC; eribulin, vinorelbine, capecitabine, or gemcitabine) until progression or unacceptable toxicity.
• Dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1, and overall survival (OS).

Results

• 732 pts were randomised (Dato-DXd: 365; ICC: 367). Median age (range) was 56 (29–86)/54 (28–86) yrs in the Dato-DXd/ICC groups. At data cut-off (17 Jul 2023), 93/39 pts in the Dato-DXd/ICC groups were ongoing treatment.
• Pts receiving Dato-DXd had significantly improved PFS vs ICC (HR 0.63 [95% CI 0.52–0.76]; p<0.0001).
• OS data were not mature; a trend for improvement favouring Dato-DXd was observed. Pts receiving Dato-DXd had lower rates of grade ≥3 TRAEs and dose reductions vs ICC 

Conclusion

• TROPION-Breast01 met the primary endpoint of PFS; the study continues to final OS. Pts receiving Dato-DXd had statistically significant and clinically meaningful improvement in PFS compared with ICC, along with a favourable and manageable safety profile.
• Results support Dato-DXd as a novel treatment option for pts with inoperable or metastatic HR+/HER2-BC who have received 1–2 prior lines of CT.

Reference

Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. 10.1016/annonc/annonc1358

Adjuvant Abemaciclib Plus Endocrine Therapy For HR+, HER2-, High-Risk Early Breast Cancer: Results from a Preplanned Monarche Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes.

Background

Two years (yrs) of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-yr treatment (tx) period in patients (pts) with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, high-risk early breast cancer (EBC).

Aim

The objective to report 5-yr efficacy results from a prespecified overall survival (OS) interim analysis.

 

Methods

• Pts were randomized (1:1) to receive ET for at least 5 yrs +/- abemaciclib for 2 yrs (tx period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN) or 1-3 ALN with Grade 3 disease and/or tumor ≥5 cm (Cohort 1).
• A smaller group of pts were enrolled with 1-3+ ALN and central Ki67 ≥20% (Cohort 2). The intent-to-treat (ITT) population consisted of Cohort 1 (5120 pts) and Cohort 2 (517 pts).
• OS in the ITT population was tested for statistical significance in the gated strategy. Hazard ratios (HR) were estimated using Cox proportional hazard model.

Results

• In the ITT population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with a HR of 0.680 (95% CI: 0.599, 0.772) for IDFS and 0.675 (95% CI: 0.588, 0.774) for DRFS.
• This persistence of abemaciclib benefit translated to continued separation of the KM curves resulting in a 5-yr absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with IDFS/DRFS rates of 6.0%/5.3% at 4 yrs and 4.8%/4.1% at 3 yrs.
• Tx benefit in Cohort 1 was consistent with ITT. No new safety signals were observed. There continued to be fewer deaths in the abemaciclib plus ET arm compared to the ET arm (208 vs 234; HR 0.903; p=0.284); significance was not met.

Conclusion

At the pivotal 5-yr mark for adjuvant EBC trials, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence well beyond the completion of tx. The increasing absolute improvement at 5 yrs is consistent with a carryover effect and further supports the use of abemaciclib in pts with high-risk EBC. OS data are evolving in favor of abemaciclib arm, and follow-up continues.

Reference

Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. 10.1016/annonc/annonc1358.

Pembrolizumab or Placebo Plus Chemotherapy Followed By Pembrolizumab or Placebo for Early-Stage TNBC: Updated EFS Results From The Phase III KEYNOTE-522 Study

Background

KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pCR and EFS with the addition of pembrolizumab (pembro) to chemotherapy (chemo) in patients (pts) with early-stage TNBC.

Aim

This study presents updated EFS results after ∼5 yr median follow-up.

Methods

• Eligible pts with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadjuvant pembro 200 mg Q3W or placebo (pbo), both given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide.
• After definitive surgery, pts received adjuvant pembro or pbo for 9 cycles or until recurrence or unacceptable toxicity. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS (time from randomization to disease progression that precluded definitive surgery, local/distant recurrence, second primary cancer, or death from any cause).

Results

• 1174 pts were randomized to pembro (n=784) or pbo (n=390).
• At data cutoff (March 23, 2023), median follow-up was 63.1 mo. 145 pts (18.5%) in the pembro group and 108 pts (27.7%) in the pbo group had an EFS event (HR 0.63 [95% CI, 0.49-0.81]).
• The 60-mo EFS rate (95% CI) was 81.3% (78.4-83.9) vs 72.3% (67.5-76.5), respectively; the median was not reached in either group.
• The most common first EFS event was distant recurrence, in 72 pts (9.2%) in the pembro group vs 55 pts (14.1%) in the pbo group.
• With 210 distant events, rates of distant disease progression- or distant recurrence-free survival at 60 mo were 84.4% with pembro vs 76.8% with pbo (HR 0.64 [95% CI, 0.49-0.84]).
• The EFS benefit with pembro was consistent across prespecified subgroups, including PD-L1 expression and nodal status. In a prespecified, non-randomized, exploratory analysis, 5-yr EFS rates in the pembro and pbo groups were 92.2% vs 88.2% in pts with a pCR, and 62.6% vs 52.3% in pts without a pCR. Follow-up for OS is ongoing.

Conclusion

Neoadjuvant pembro + chemo followed by adjuvant pembro continues to show a clinically meaningful improvement in EFS compared with neoadjuvant chemo alone in pts with early-stage TNBC, regardless of the pCR outcome.

 

Reference

Annals of Oncology (2023) 34 (suppl_2): S1254-S1335. 10.1016/annonc/annonc1358.

Efficacy and Safety of Trastuzumab with or without A Tyrosine Kinase Inhibitor for HER2-positive Breast Cancer: A Systematic Review and Meta-Analysis

Background

This study aimed to explore whether the combination of trastuzumab and small molecule tyrosine kinase inhibitor (TKI) can further improve the efficacy of HER2-positive breast cancer without adding additional adverse events.

Method

• PubMed, Embase, Cochrane, and Web of Science were systematically searched for relevant articles from inception until Nov 2022.
• Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Subgroup analyses were performed based on disease status and TKI types.

Results

• A total of 10,623 patients from 16 studies were included in this meta-analysis. Trastuzumab combined with TKI dual-target blockade showed significant improvement in PFS and OS compared with trastuzumab single-targeted therapy.
• A random-effects model was applied, and the pooled HR was 0.52 (95% CI: 0.41–0.66, P<0.001), suggesting that trastuzumab plus TKI was highly associated with better PFS. Further subgroup analysis of the different TKI agents (including lapatinib, pyrotinib, and tucatinib) showed that combination therapy was related to better PFS in all subgroups.
• In the metastatic setting, patients receiving trastuzumab combined with TKI had significantly longer OS than those receiving trastuzumab monotherapy (HR=0.71, 95% CI: 0.58–0.87, P=0.001).
• Besides, higher objective response rate was observed with trastuzumab plus TKI (OR=2.17, 95% CI: 1.34–3.50, P=0.002). Patients receiving combination therapy had a higher incidence of discontinuation, and grade ≥3 diarrhea.

Conclusion

In summary, combining TKI with trastuzumab confers a significant improvement in clinical outcomes with tolerable toxicity for individuals with HER2-positive breast cancer, especially in advanced settings. The different efficacies of TKIs combined with trastuzumab may be related to the mechanism of action of the different TKIs.

Reference

Annals of Oncology (2023) 34 (suppl_2): S334-S390. 10.1016/annonc/annonc1299

The Characteristics of HER2-positive Microinvasive Breast Cancer And The Necessity Of Chemotherapy And Anti-HER2 Therapy in These Patients: A Real-World Study

Background

The prognosis of microinvasive breast cancer (MIBC) is between ductal carcinoma in situ and T1aN0 stage tumors.

Aim

This real-world study to explore the prognosis of human epidermal factor receptor 2 (HER2)-positive MIBC, as well as to find out whether chemotherapy and anti-HER2 therapy could improve outcome in this population.

Methods

• Patients who received radical surgery and were diagnosed with lymph node-negative HER2-positive MIBC at the National Cancer Center in China from January 2010 to December 2019 were consecutively enrolled.
• The invasive components were confirmed HER2-positive by pathologists from our center. The exclusion criteria included: 1) distant metastasis before surgery; 2) HER2 status of the invasive components was unknown. Clinicopathologic characteristics and follow-up outcome data were collected.

Results

• A total of 121 patients were included. The median age was 51 years old, and the median follow-up time was 68.3 months.
• Twenty-four patients (19.8%) received adjuvant chemotherapy (CT), of which 7 patients received CT combined with trastuzumab.
• Among these 24 patients, 17 patients were aged ≤ 50, and 20 patients were estrogen receptor (ER) negative. In total, 5 patients experienced recurrence (2 in situ breast recurrence, 3 distant metastasis), all within 3 years after surgery.
• The 3-year disease free survival (DFS) rate and 5-year DFS rate were all 95.9%. Univariate analysis showed that patients aged ≤ 50 might have worse outcomes than those aged > 50 (5-year DFS rate 92.5% versus 98.5%, p=0.098).
• Using propensity score matching, patients who received CT with or without trastuzumab were matched with those who did not receive CT in a 1:2 ratio based on age and ER status. Patients who received CT with or without trastuzumab showed a trend of increase in 5-year DFS rate compared to those who did not receive CT (100% vs 89.6%, p=0.106).

Conclusions

HER2-positive MIBC had a relatively good prognosis. For patients with risk factors of relapse, CT and trastuzumab might decrease recurrence, so adjuvant CT and anti-HER2 therapy could be considered in this population.

Reference

Annals of Oncology (2023) 34 (suppl_2): S278-S324. 10.1016/annonc/annonc1297

Palbociclib Plus Endocrine Therapy in HR+/HER2- Advanced Breast Cancer Patients: Interim Results of The PERFORM Study

Background

• CDK4/6 inhibitors plus endocrine therapy (ET) are the first-line (1L) standard for patients (pts) with HR+/HER2- advanced breast cancer (ABC). Data from clinical trials have shown high efficacy and good tolerability.
• Real World Studies are important to support these data and close potential knowledge gaps.

Methods

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. In this second interim analysis (IA 2), response rates and dose modifications in the total population and in age-related subgroups (≥75 years vs <75 years) were investigated.

Results

• Between 10/2020 and 09/2022, 938 pts were enrolled and 624 pts had a follow-up of >6 months and were evaluable for analysis.
• The median age was 68 years (range 33-89), 39% of pts had de novo ABC and 11% ECOG ≥2, at inclusion. 30% of patients were ≥75 years of age.
• Of these, 22% had an ECOG performance status of ≥2 at inclusion compared to 7% of pts <75 years. The rate of de novo ABC was higher in pts ≥75 years (44%) than pts <75 years (36%), whereas the number and distribution of metastases was comparable.
• 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.
• Notably PFS, ORR and CBR were consistent across age groups. Dose modifications were performed in 74.1% of pts ≥75 years vs 61.5% of pts <75 years, respectively; >70% of pts in both subgroups are still on study treatment. Treatment discontinuation rates were comparable in both age groups (28.6% ≥75 years vs 27.3% <75 years), but (serious) adverse event as reason for treatment discontinuation was more frequent in pts ≥75 years (9.2% vs 3.0%).

Conclusions

• 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.
• These findings are in line with the data of clinical trials and support use of palbociclib based treatment independent of age.

Reference

Annals of Oncology (2023) 34 (suppl_2): S334-S390. 10.1016/annonc/annonc1299