Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij borstkanker van arts-bioloog drs. Engelbert Valstar

30 mei 2020: Bron: ASCO 2020:

Hier een aantal aanbevolen abstracten over borstkanker door artsen die zelf voor ASCO werken. Klik op de nummers voor de abstracten. Het zijn veel abstracten want door maar liefst vier verschillende oncologen / artsen zijn lijsten gemaakt.

Aanbevolen door Dr. Benjamin Anderson

Plenary Session: Breast Cancer—Local/Regional/Adjuvant

LBA2 A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). SA Khan, F Zhao, LJ Solin, et al

Take-Home Message

  • This randomized trial will provide important and possibly definitive information regarding the value of local control of disease with surgical therapy when patients initially present with stage IV disease.
  • From the perspective of a breast surgeon, this presentation will be a highlight of the meeting.

Session: Breast Cancer—Local/Regional/Adjuvant

DCIS

519 Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ (DCIS): Comparison of patients with and without index surgery. MD Ryser, L Hendrix, SM Thomas, et al

Take-Home Message

  • Genomic methods continue to be explored to help find the DCIS patients who may not warrant radiation therapy. Studies continue to indicate that a subgroup of non–high grade DCIS patients are being overtreated, although prospective identification of these favorable biology cancers continues to be difficult.
  • The abstract suggests that, among patients in the surveillance group, up to 10% developed an ipsilateral invasive breast cancer at 8 years. Is that really a low-risk group?

Low- and Middle-Income Countries

e12508 Breast cancer recurrence rate in patients treated for early breast cancer. C Munguti, MC Mutebi, M Ng'ang'a, et al

Take-Home Message

  • It has been debated whether Western cancer-outcome metrics can be reproduced in sub-Saharan Africa, where mammographic screening is largely unavailable or inaccessible. This Kenyan study from Aga Khan University Hospital demonstrates that similarly locoregional control rates can be achieved among patients presenting with early-stage disease, even when the primary mode of detection is clinical breast examination (CBE) rather than mammographic screening.
  • This also supports the position of the World Health Organization (WHO) that early diagnotic approaches (detecting and diagnosing symptomatic breast cancers when they are still at early stages) is a viable strategy for sub-Saharan Africa.

568 Validation of nomograms to predict non-sentinel lymph node metastasis after positive sentinel lymph node in breast cancer: Indian cohort background. A Reddy, NS Nair, S Mokal, et al

Take-Home Study

  • This study indicates that Western nomograms predicting sentinel node outcomes don’t perform well in an India population.
  • It is important to remind ourselves that the prediction tools we use within certain groups may lack accuracy in populations where significant healthcare delivery issues influence patient presentation and stage at diagnosis.

Locoregional Impact of Neoadjuvant Chemotherapy

572 Impact of axillary lymph node dissection (ALND) on survival in patients with ypN1 breast cancer that receive regional nodal irradiation (RNI): A national cancer database (NCDB) analysis. M Kharouta, N Damico, EE Harris, JA Lyons

Take-Home Message

  • This population-based study supports the indications that complete axillary node dissection (ALND) in addition to regional nodal irradiation is not associated with increased survival, reinforcing the importance and value of the upcoming randomized trials.
  • Our goal is to minimize the use of ALND when it can be safely avoided, given the high rates of lymphedema associated with this procedure.

581 The impact of pattern of tumor response and other post-treatment histologic features on local recurrence in patients treated with neoadjuvant chemotherapy and breast conservation. A Laws, RG Pastorello, J Choi, et al

Take-Home Message

  • This study examines patterns of locoregional failure following neoadjuvant chemotherapy.
  • It shows that modern systemic therapy assists well in promoting local control in the breast, where only 5% of patients suffered a local recurrence at 6 years.

Aanbevolen door Lee Schwartzberg, MD

Plenary Session: Breast Cancer—Local/Regional/Adjuvant

LBA2 A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). SA Khan, F Zhao, LJ Solin, et al

Take-Home Message

  • Results are pending, but eagerly awaited.
  • These results will undoubtedly shed some light on the best way to manage the primary tumor when patients present with metastatic disease, a situation without a lot of quality data to base decisions on.

Session: Breast Cancer—Local/Regional/Adjuvant

500 Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC). N Harbeck, S-A Im, CH Barrios, et al

Take-Home Message

  • Negative trial.
  • The control remains the standard of care.

501 Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. A van der Voort, MS van Ramshorst, ED van Werkhoven, et al

Take-Home Message

  • No benefit for anthracycline was found in this phase III trial, and there was more toxicity.
  • The non-anthracycline standard in patients with stage II/III breast cancer consists of neoadjuvant chemotherapy plus dual anti-HER2 blockade.

506 MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. F Cardoso, L van't Veer, C Poncet, et al

Take-Home Message

  • In this 8-year follow-up of MINDACT, there was no difference in clinical high-risk/genomic low-risk (by 70 gene assay) chemotherapy-untreated patients from the 5-year outcome in terms of the primary endpoint of distant metastasis–free survival.
  • That primary endpoint at 5 years continues to be met, with a 2.6% absolute gain in the need for chemotherapy at 8 years. Is 2.6% a small-enough percentage to forego chemo or not? Still an open question.

507 Phase III trial of metronomic capecitabine maintenance after standard treatment in operable triple-negative breast cancer (SYSUCC-001). XI Wang, S-S Wang, H Huang, et al

Take-Home Message

  • Maintenance capecitabine therapy improved distant disease–free survival after standard therapy. These results confirm the CREATE-X benefit after neoadjuvant chemotherapy in patients with less than a pCR.
  • Should it be given to all patients? We await the full analysis.

Session: Breast Cancer—Metastatic

1000 KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Cortes, DW Cescon, HS Rugo, et al

Take-Home Message

  • There was a benefit in terms of progression-free survival with pembrolizumab in patients with a combined positive score for PD-L1 expression of >10%.
  • We await details to see if different chemo backbones show a similar benefit.

1001 Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). P Sharma, E Rodler, WE Barlow, et al

Take-Home Message

  • Patients with BRCA-like triple-negative breast cancer had improved progression-free survival from the combination of veliparib and cisplatin.

1002 TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). NM Tung, ME Robson, S Ventz, et al

Take-Home Message

  • In this proof of principle study, PARP inhibitor olaparib monotherapy showed a clinically meaningful response in patients with metastatic breast cancer with somatic BRCA1/2 or germline PALB2 mutations but not in those with ATM or CHEK2 mutations.

1005 Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). NU Lin, RK Murthy, CK Anders, et al

Take-Home Message

  • In this cohort of the HER2CLIMB trial, the results of the exploratory efficacy analyses of tucatinib added to trastuzumab and capecitabine in HER2-positive patients with brain metastases are reported.
  • There was a large improvement in brain events with the addition of tucatinib, a 67% reduction in the risk CNS progression, and prolonged overall survival.

1006 Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with PIK3CA-mutated (mut) hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) previously treated with cyclin-dependent kinase 4/6 inhibitor (CDKi) + aromatase inhibitor (AI): BYLieve study results. HS Rugo, F Lerebours, E Ciruelos, et al

Take-Home Message

  • Results of this study support the use of alpelisib plus fulvestrant for patients with HR+, HER2– PIK3CA-mutated advanced breast cancer who were previously treated with CKD4/6 and aromatase inhibitors.
  • The clinical benefit rate of 50.4% supports use of this regimen after progression on CDK 4/6.

1007 PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[-] metastatic breast cancer. MR Borrego, J Gavilá, M Sampayo-Cordero, et al

Take-Home Message

  • Palbociclib plus fulvestrant did not improve progression-free survival compared with palbociclib plus letrozole in this group of patients with endocrine-sensitive HR+, HER2− metastatic breast cancer, and 41% had de novo metastatic disease.
  • It will be interesting to see results by ESR1 mutation, if a trial is done.

Vervolg aanbevolen abstracten voor borstkanker van ASCO 2020

Aanbevolen door Sara M. Tolaney MD, MPH

Session: Breast Cancer—Metastatic

1000 KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Cortes, DW Cescon, HS Rugo, et al

Take-Home Message

  • Patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or placebo and chemotherapy. Pembrolizumab use was associated with significantly improved progression-free survival compared with placebo in patients with tumors with high PD-L1 expression. There was no significant difference between the two groups in the rate of grade 3–5 treatment-related adverse events.
  • Pembrolizumab was well-tolerated and showed promising clinical activity in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer with high PD-L1 expression.

1002 TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). NM Tung, ME Robson, S Ventz, et al

Take-Home Message

  • Patients with metastatic breast cancer with progression on no more than two metastatic chemotherapy regimens were treated with olaparib monotherapy until progression or unacceptable toxicity. The objective response rate was 29.6% in patients with germline mutations in non–BRCA1/2 DDR-pathway genes and 38.5% in those with somatic mutations in non–BRCA1/2 DDR-pathway genes or BRCA1/2. The genetic signature predicted the response, with a high response rate seen in those with gPALB2 and sBRCA mutations; no responses were seen in patients with a solitary CHEK2 or ATM mutation. Some responses have been durable beyond 16 months.
  • Olaparib monotherapy showed activity in patients with metastatic breast cancer and sBRCA1/2 or gPALB2 mutations. Final data regarding response rates and secondary endpoints are awaited.

1005 Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). NU Lin, RK Murthy, CK Anders, et al

Take-Home Message

  • The authors report the results of an exploratory analyses of the HER2CLIMB trial to evaluate the efficacy of the highly selective HER2 kinase inhibitor tucatinib in patients with HER2+ metastatic breast cancer with brain metastases. Patients were randomized to receive either tucatinib or placebo in conjunction with trastuzumab and capecitabine. The median CNS progression-free survival was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. There was a 42% reduction in the risk of death in the tucatinib arm, with a hazard ratio of 0.58 for overall survival compared with the placebo arm (P = .005). The intracranial confirmed objective response rate was 47.3% in the tucatinib arm versus 20.0% in the placebo arm. Among a group of 30 patients with isolated brain progression who continued therapy after local treatment, there was a 67% decrease in the risk of second progression or death.
  • The combination of tucatinib plus trastuzumab and capecitabine may become the standard of care among patients with HER2+ metastatic breast cancer with brain metastases.

1007 PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[-] metastatic breast cancer. MR Borrego, J Gavilá, M Sampayo-Cordero, et al

Take-Home Message

  • Investigators aimed to identify the best endocrine agent to combine with palbociclib in the first-line treatment of patients with luminal metastatic breast cancer. A total of 486 patients with ER-positive / HER2-negative metastatic breast cancer, no prior therapy in the advanced setting, and endocrine-sensitive criteria were randomized to palbociclib + fulvestrant or palbociclib + letrozole. The primary endpoint was progression-free survival. Median progression-free survival with palbociclib + fulvestrant was 27.9 months versus 32.8 months with palbociclib + letrozole (HR, 1.1; P = .321). Grade ≥3 adverse events were similar in both arms.
  • Palbociclib + fulvestrant did not improve progression-free survival compared with palbociclib + letrozole in this group of patients. However, both arms demonstrated comparable 4-year overall survival (a secondary endpoint). Therefore, palbociclib + fulvestrant is a reasonable alternative to palbociclib + letrozole in these patients.

Session: Breast Cancer—Local/Regional/Adjuvant

502 Biomarker data from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer. C Denkert, C Lambertini, PA Fasching, et al

Take-Home Message

  • These investigators conducted an exploratory analysis of potential biomarkers of treatment response in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer randomized to receive adjuvant trastuzumab emtansine (T-DM1) or trastuzumab. PIK3CA mutation status was not associated with outcomes in either treatment arm. The clinical benefit of T-DM1 over trastuzumab was observed across all single-gene and immune gene-signature subgroups. In the trastuzumab treatment arm only, high versus low HER2 expression was associated with less favorable outcomes while high versus low PD-L1 expression was associated with more favorable outcomes.
  • The benefit associated with the use of T-DM1 in this population appeared to be independent of all the biomarkers assessed.

508 Primary results of NRG Oncology / NSABP B-43: Phase III trial comparing concurrent trastuzumab (T) and radiation therapy (RT) with RT alone for women with HER2-positive ductal carcinoma in situ (DCIS) after lumpectomy. R Rabinovitch, DS Parda, SA Seaward, et al

Take-Home Message

  • Women with ductal carcinoma in situ (DCIS) resected by lumpectomy were randomized to receive radiation therapy (RT) alone or concurrent trastuzumab (T) and RT. The hazard ratio for the risk of ipsilateral breast tumor recurrence (IBTR) in the T+RT group compared with the RT-alone group was 0.81 (P = .26). The annual IBTR event rate was 0.99% per year in the RT group versus 0.80% per year in the RT+T group.
  • The addition of T to RT was associated with a modest and nonsignificant reduction in the risk of IBTR compared with RT alone, but this did not meet the protocol objective of a reduction of 36%.

Aanbevolen door dr. Reshma L. Mahtani DO

Session: Breast Cancer—Local/Regional/Adjuvant

500 Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC). N Harbeck, S-A Im, CH Barrios, et al

Take-Home Message

  • The KAITLIN study enrolled 1846 patients with HER2-positive early breast cancer. Within 9 weeks following surgery, patients were treated with anthracycline-based chemotherapy and then randomized to one of two regimens: T-DM1 + pertuzumab (AC-KP) or taxane + concurrent trastuzumab + pertuzumab (AC-THP). Co-primary endpoints were invasive disease–free survival (IDFS) in the lymph node–positive group and in the intention-to-treat population. Neither of the co-primary endpoints were achieved. In lymph node–positive patients, the 3-year IDFS rate with AC-KP was 94.1% versus 92.7% in the AC-THP group. In the intention-to-treat population, the 3-year IDFS rate with AC-KP was 94.2% versus 93.1% with AC-THP.
  • T-DM1 in lieu of adjuvant taxane + trastuzumab did not improve efficacy or safety.

503 Chemotherapy (CT) de-escalation using an FDG-PET/CT (F-PET) and pathological response-adapted strategy in HER2[+] early breast cancer (EBC): PHERGain Trial. J Cortes, G Gebhart, MR Borreg, et al

Take-Home Message

  • The PHERGain trial randomized patients with HER2+ stage I–III early breast cancer to different treatment regimens of trastuzumab plus pertuzumab (HP) in a response-adapted strategy to determine if identifying markers of response to HP could help de-escalate chemotherapy. The trial assessed early metabolic response to neoadjuvant HP via FDG-PET prior to and after two cycles of treatment.
  • The results show that FDG-PET identifies patients who are more likely to benefit from chemotherapy-free dual HER2-blockade with HP. Depending on the results of the 3-year invasive disease-free survival endpoint, this strategy could select a group of patients who do not need chemotherapy.

506 MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. F Cardoso, L van't Veer, C Poncet, et al

Take-Home Message

  • The prospective phase III randomized MINDACT study enrolled 6693 women with early-stage breast cancer between 2007 and 2011. The distant metastasis–free survival (DMFS) rate at 5 years was assessed in the primary test population of clinical high-risk/genomic low-risk (C-High / G-Low) patients who were randomized to receive no adjuvant chemotherapy (CT). A secondary analysis assessed DMFS and overall survival in the intention-to-treat population of the C-High / G-Low group randomized to CT versus no CT. Median follow-up was 8.7 years, yielding an updated DMFS rate of 95.1% for the primary test population of C-High / G-Low patients with no CT. For the intention-to-treat population of C-High / G-Low patients, the DMFS is 92.0% with CT and 89.4% without CT.
  • The primary DMFS endpoint continues to be met in C-High– / G-Low–risk women who forego adjuvant chemotherapy, confirming MINDACT as a positive de-escalation study. The 70-gene signature MammaPrint test maintains level IA evidence supporting its clinical utility for decision-making regarding adjuvant chemotherapy.

507 Phase III trial of metronomic capecitabine maintenance after standard treatment in operable triple-negative breast cancer (SYSUCC-001). XI Wang, S-S Wang, H Huang, et al

Take-Home Message

  • This phase III trial enrolled 434 patients with operable triple-negative breast cancer who were randomized to metronomic capecitabine as maintenance therapy versus observation following standard treatment for curative intent. The primary endpoint was disease-free survival. The capecitabine group had significantly better 5-year survival rates compared with observation (83% vs 73%). A 1-year course of capecitabine was completed by 91.4% of patients.
  • Metronomic capecitabine as maintenance therapy for 1 year following standard treatment significantly improved disease-free survival in operable triple-negative breast cancer. The regimen was safe and well-tolerated.

512 Breast cancer index (BCI) predicts benefit of two-and-a-half versus five years of extended endocrine therapy in HR+ breast cancer patients treated in the ideal trial. G-Jan L, I Noordhoek, K Treuner, et al

Take-Home Message

  • BCI (H/I) is a biomarker based on gene expression. This study assessed how well BCI (H/I) predicted the endocrine benefit of 2.5 versus 5 years of extended letrozole in the IDEAL trial. The study included 908 postmenopausal HR+ breast cancer patients with available tumor specimens; 88% had received prior treatment with an aromatase inhibitor–based therapy. The primary endpoint was the recurrence-free interval (RFI). BCI (H/I) was strongly correlated with response to extended letrozole in the overall cohort and in the pN+ cohort. BCI also predicted extended endocrine treatment benefit in patients who received any primary adjuvant therapy based on an aromatase inhibitor.
  • The study’s new finding is that BCI (H/I) predicts benefit from extended letrozole in postmenopausal patients treated with primary adjuvant therapy based on an aromatase inhibitor. There is a growing body of evidence that BCI (H/I) status predicts endocrine response in distinct subgroups of patients.

517 Comprehensive profiling of androgen receptor-positive (AR+) triple-negative breast cancer (TNBC) patients (pts) treated with standard neoadjuvant therapy (NAT) +/- enzalutamide. B Lim, S Seth, L Huo, et al

Take-Home Message

  • The ARTEMIS nonrandomized trial was conducted to evaluate whether standard neoadjuvant therapy (NAT) can be used to personalize therapy. After four cycles of doxorubicin-based NAT, patients with insensitive disease by imaging were offered clinical trials as the second phase of NAT, based upon molecular profiling of pretreatment biopsies. In the study, 17 patients with triple-negative breast cancer insensitive to doxorubicin-based NAT were treated with enzalutamide plus paclitaxel. From this group, 5 of 15 (33%) responded to treatment. All responders had an upregulated androgen response pathway as measured by transcriptomic analysis from the pretreatment biopsies.
  • Among patients with triple-negative breast cancer insensitive to doxorubicin-based NAT, those with a luminal androgen receptor subtype and baseline upregulated androgen response pathway may benefit from treatment with enzalutamide plus paclitaxel, possibly through P13K targeting.

523 Does chemotherapy affect survival of breast cancer (BC) patients with recurrence score 26-30? S Goranta, E Drizik, UT Omaduvie, et al

Take-Home Message

  • Investigators retrospectively evaluated the effect of adjuvant chemotherapy on breast cancer–specific survival. Newly diagnosed female breast cancer patients with T1-T3, HR-positive, HER2-negative, and lymph node–negative breast cancer with recurrence score of 26–30 were identified from the SEER database; 56.5% were treated with adjuvant chemotherapy. The group had an overall 5-year breast cancer–specific survival of 97.3%.
  • After adjustment, adjuvant chemotherapy did not have an effect on survival. There was no effect on survival in patients younger than 50 years or 50 years and older.

Session: Breast CancerMetastatic

1000 KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Cortes, DW Cescon, HS Rugo, et al

Take-Home Message

  • Patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or placebo and chemotherapy. Pembrolizumab use was associated with significantly improved progression-free survival compared with placebo in patients with tumors with high PD-L1 expression. There was no significant difference between the two groups in the rate of grade 3–5 treatment-related adverse events.
  • Pembrolizumab was well-tolerated and showed promising clinical activity in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer with high PD-L1 expression.

1001 Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416). P Sharma, E Rodler, WE Barlow, et al

Take-Home Message

  • This phase II randomized trial compared the efficacy of cisplatin plus the PARP inhibitor veliparib versus placebo in three groups of patients with metastatic breast cancer: gBRCA+, BRCA-like, and non–BRCA-like. The primary endpoint was progression-free survival. In the BRCA-like group, progression-free survival was improved with veliparib compared with placebo (median, 5.7 vs 4.3 months; 1-year PFS 20% vs 7%).
  • Among patients with BRCAwt triple-negative breast cancer, biomarkers identified a subgroup of patients (BRCA-like) who benefited from the addition of veliparib to cisplatin.

1002 TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). NM Tung, ME Robson, S Ventz, et al

Take-Home Message

  • Patients with metastatic breast cancer with progression on no more than two metastatic chemotherapy regimens were treated with olaparib monotherapy until progression or unacceptable toxicity. The objective response rate was 29.6% in patients with germline mutations in non–BRCA1/2 DDR-pathway genes and 38.5% in those with somatic mutations in non–BRCA1/2 DDR-pathway genes or BRCA1/2. The genetic signature predicted the response, with a high response rate seen in those with gPALB2 and sBRCA mutations; no responses were seen in patients with a solitary CHEK2 or ATM mutation. Some responses have been durable beyond 16 months.
  • Olaparib monotherapy showed activity in patients with metastatic breast cancer and sBRCA1/2 or gPALB2 mutations. Final data regarding response rates and secondary endpoints are awaited.

1003 Pyrotinib or lapatinib plus capecitabine for HER2+ metastatic breast cancer (PHOEBE): A randomized phase III trial. B Xu, M Yan, F Ma, et al

Take-Home Message

  • Patients with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes and/or anthracyclines were randomized to receive pyrotinib or lapatinib, and both arms received concomitant capecitabine. The median progression-free survival (PFS) was 12.5 months in the pyrotinib arm versus 6.8 months in the lapatinib arm (HR, 0.39; P < .0001). Common grade 3+ adverse events included diarrhea and hand–foot syndrome.
  • Pyrotinib plus capecitabine was associated with significantly improved PFS compared with lapatinib and capecitabine in patients with pretreated HER2+ metastatic breast cancer.

1005 Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). NU Lin, RK Murthy, CK Anders, et al

Take-Home Message

  • The authors report the results of an exploratory analyses of the HER2CLIMB trial to evaluate the efficacy of the highly selective HER2 kinase inhibitor tucatinib in patients with HER2+ metastatic breast cancer with brain metastases. Patients were randomized to receive either tucatinib or placebo in conjunction with trastuzumab and capecitabine. The median CNS progression-free survival was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. There was a 42% reduction in the risk of death in the tucatinib arm, with a hazard ratio of 0.58 for overall survival compared with the placebo arm (P = .005). The intracranial confirmed objective response rate was 47.3% in the tucatinib arm versus 20.0% in the placebo arm. Among a group of 30 patients with isolated brain progression who continued therapy after local treatment, there was a 67% decrease in the risk of second progression or death.
  • The combination of tucatinib plus trastuzumab and capecitabine may become the standard of care among patients with HER2+ metastatic breast cancer with brain metastases.

1007 PARSIFAL: A randomized, multicenter, open-label, phase II trial to evaluate palbociclib in combination with fulvestrant or letrozole in endocrine-sensitive patients with estrogen receptor (ER)[+]/HER2[-] metastatic breast cancer. MR Borrego, J Gavilá, M Sampayo-Cordero, et al

Take-Home Message

  • Investigators aimed to identify the best endocrine agent to combine with palbociclib in the first-line treatment of patients with luminal metastatic breast cancer. A total of 486 patients with ER-positive, HER2-negative metastatic breast cancer, no prior therapy in the advanced setting, and endocrine-sensitive criteria were randomized to palbociclib plus fulvestrant or palbociclib plus letrozole. The primary endpoint was progression-free survival. The median progression-free survival with palbociclib plus fulvestrant was 27.9 months versus 32.8 months with palbociclib plus letrozole (HR, 1.1; P = .321). Grade >3 adverse events were similar in both arms.
  • Palbociclib plus fulvestrant did not improve progression-free survival compared with palbociclib plus letrozole in this group of patients. However, both arms demonstrated comparable 4-year overall survival (a secondary endpoint). Therefore, palbociclib plus fulvestrant is a reasonable alternative to palbociclib plus letrozole in these patients.

1013 Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119. EP Winer, O Lipatov, S-A Im, et al

Take-Home Message

  • Investigators assessed the association of tumor mutational burden with the efficacy of pembrolizumab monotherapy versus chemotherapy in patients with previously treated metastatic triple-negative breast cancer. Patients with triple-negative disease and one or two prior systemic treatments for metastatic disease were enrolled and randomized to pembrolizumab or single-agent chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine). Of 26 patients whose tumor mutational burden was >10 mut/Mb, the objective response rate was 14.3% with pembrolizumab and 8.3% with chemotherapy. In patients with a tumor mutational burden <10, the objective response rate was similar with pembrolizumab and chemotherapy (12.7% vs 12.8%).
  • These data suggest a possible association between tumor mutational burden and clinical benefit with pembrolizumab but not chemotherapy in this group of patients.

1036 Trastuzumab deruxtecan for HER2-positive metastatic breast cancer: DESTINY-Breast01 subgroup analysis. S Modi, F Andre, IE Krop, et al

Take-Home Message

  • This post hoc study of the DESTINY-Breast01 trial used multivariate analysis with logistic regression models and Cox proportional hazards models to explore 15 relevant clinical predictor variables of response to trastuzumab deruxtecan. Hormone receptor–positive status, fewer prior treatment regimens, pertuzumab given in the first or second line, and normal renal and hepatic function were all associated with an improved objective response rate, duration of response, or median progression-free survival.
  • Trastuzumab deruxtecan demonstrated strong efficacy in all clinical subgroups. Further study of the clinical and molecular variables affecting efficacy may be merited.

1060 Meta-analysis of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy versus endocrine therapy alone on progression-free survival (PFS) and overall survival (OS) for metastatic breast cancer (MBC). R Kunwor, R Baniya, MM Abu-Khalaf, et al

Take-Home Message

  • This meta-analysis evaluated progression-free survival and overall survival with three CDK 4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—used in HR+/HER2− metastatic breast cancer. The meta-analysis included 8 phase II and III randomized controlled trials (RCTs) comparing CKD4/6 inhibitors plus endocrine therapy versus endocrine therapy alone in a total of 4338 patients with HR+/HER2− metastatic disease. The pooled hazard ratio for progression-free survival in the 8 RCTs was 0.55 (P < .00001). The pooled hazard ratio for overall survival in the 8 RCTs was 0.75 (P < .00001).
  • The meta-analysis confirmed the enhanced progression-free survival benefit of CDK 4/6 inhibitors plus endocrine therapy. The pooled hazard ratio of all 8 RCTs showed an overall survival benefit.

Aanbevolen door Prof. Lillie Shockney

Session: Breast Cancer—Metastatic

1000 KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Cortes, DW Cescon, HS Rugo, et al

Take-Home Message

  • Patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or placebo and chemotherapy. Pembrolizumab use was associated with significantly improved progression-free survival compared with placebo in patients with tumors with high PD-L1 expression. There was no significant difference between the two groups in the rate of grade 3–5 treatment-related adverse events.
  • Pembrolizumab was well-tolerated and showed promising clinical activity in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer with high PD-L1 expression.

1002 TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). NM Tung, ME Robson, S Ventz, et al

Take-Home Message

  • Patients with metastatic breast cancer with progression on no more than two metastatic chemotherapy regimens were treated with olaparib monotherapy until progression or unacceptable toxicity. The objective response rate was 29.6% in patients with germline mutations in non–BRCA1/2 DDR-pathway genes and 38.5% in those with somatic mutations in non–BRCA1/2 DDR-pathway genes or BRCA1/2. The genetic signature predicted the response, with a high response rate seen in those with gPALB2 and sBRCA mutations; no responses were seen in patients with a solitary CHEK2 or ATM mutation. Some responses have been durable beyond 16 months.
  • Olaparib monotherapy showed activity in patients with metastatic breast cancer and sBRCA1/2 or gPALB2 mutations. Final data regarding response rates and secondary endpoints are awaited.

1003 Pyrotinib or lapatinib plus capecitabine for HER2+ metastatic breast cancer (PHOEBE): A randomized phase III trial. B Xu, M Yan, F Ma, et al

Take-Home Message

  • Patients with HER2+ metastatic breast cancer previously treated with trastuzumab and taxanes and/or anthracyclines were randomized to receive pyrotinib or lapatinib, and both arms received concomitant capecitabine. The median progression-free survival (PFS) was 12.5 months in the pyrotinib arm versus 6.8 months in the lapatinib arm (HR, 0.39; P < .0001). Common grade 3+ adverse events included diarrhea and hand–foot syndrome.
  • Pyrotinib plus capecitabine was associated with significantly improved PFS compared with lapatinib and capecitabine in patients with pretreated HER2+ metastatic breast cancer.

1005 Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). NU Lin, RK Murthy, CK Anders, et al

Take-Home Message

  • The authors report the results of an exploratory analyses of the HER2CLIMB trial to evaluate the efficacy of the highly selective HER2 kinase inhibitor tucatinib in patients with HER2+ metastatic breast cancer with brain metastases. Patients were randomized to receive either tucatinib or placebo in conjunction with trastuzumab and capecitabine. The median CNS progression-free survival was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. There was a 42% reduction in the risk of death in the tucatinib arm, with a hazard ratio of 0.58 for overall survival compared with the placebo arm (P = .005). The intracranial confirmed objective response rate was 47.3% in the tucatinib arm versus 20.0% in the placebo arm. Among a group of 30 patients with isolated brain progression who continued therapy after local treatment, there was a 67% decrease in the risk of second progression or death.
  • The combination of tucatinib plus trastuzumab and capecitabine may become the standard of care among patients with HER2+ metastatic breast cancer with brain metastases.

1008 Randomized trial of a collaborative palliative and oncology care intervention to improve communication about end-of-life care in patients with metastatic breast cancer. JS Temel, B Moy, AE-Jawahri, et al

Take-Home Message

  • Patients with metastatic breast cancer and clinical indicators of a poor prognosis were randomized to receive collaborative palliative and oncology care with five structured palliative care visits or standard care. The rate of documented end-of-life care discussions was 67.2% in the intervention group versus 40.7% in the group receiving usual care (P = .006). There was no difference in reported quality of life or mood between the two groups.
  • The use of this new model improved communication and documentation of end-of-life discussions, and further study is warranted to evaluate the impact on subsequent healthcare utilization.

E13052 Comparison of treatment-related adverse events (TRAE) of different CDK4/6 inhibitors (CDK4/6i) in metastatic breast cancer (MBC): A network meta-analysis. A Desnoyers, M Nadler, V Kumar, et al

Take-Home Message

  • The authors of this meta-analysis of seven randomized controlled trials compared the treatment-related adverse events associated with the three CDK4/6 inhibitors used in the treatment of metastatic breast cancer. Ribociclib and abemaciclib were associated with less grade 3/4 hematological toxicity but more gastrointestinal toxicity than palbociclib. The rate of treatment discontinuation was highest with abemaciclib. The efficacy of the three agents was comparable.
  • Compared with palbociclib and ribociclib, abemaciclib was associated with higher rates of treatment discontinuation possibly due to gastrointestinal toxicity.

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