ESMO consensus guidelines for advanced breast cancer

ESMO has published updated consensus guidelines for advanced breast cancer. Key new recommendations are summarised below.

ER positive / HER-2 negative metastatic breast cancer (MBC)

CDK4/6 inhibitors:

• CDK4/6 inhibitor with endocrine therapy is the standard of care for patients with ER+/HER-2 neg ABC, and can be combined with an aromatase inhibitor (AI) or fulvestrant in de novo or recurrent ABC, in the first- or second-line, and in cases of primary or secondary resistance.
• The ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scores for the use of a CDK4/6 inhibitor combined with endocrine therapy for ABC patients are:
  • Palbociclib + AI 1st line: Efficacy score: 3 (PFS); No improved QoL; ESMO-MCBS: 3.
  • Abemaciclib + AI 1st line: Efficacy score: 3 (PFS); No QoL reported; ESMO-MCBS: 3.
  • Ribociclib + AI 1st line post-menopausal: Efficacy score: 3 (PFS); No improved QoL; ESMO-MCBS: 3.
  • Ribociclib + endocrine therapy (ET) 1st line pre-menopausal: Efficacy score: 4 (PFS&OS); Improved QoL; ESMO-MCBS: 5.
  • Palbociclib + fulvestrant 2nd line: Efficacy score: 3 (PFS&OS); Improved QoL; ESMO-MCBS: 4.
  • Ribociclib + fulvestrant (1st , 2nd line): Efficacy score: 4 (PFS&OS); No improvement in QoL; ESMOMCBS: 4.
  • Abemaciclib + fulvestrant 2nd line: Efficacy score: 4 (PFS&OS); No QoL benefit; ESMO-MCBS: 4.
• Guidelines panelists preferred CDK4/6 inhibitor in the first-line setting for the majority of patients.

• Alpelisib with fulvestrant is an option for patients with PIK3CA-mutant tumours (in exons 9 or 20), previously exposed to an AI and with appropriate HbA1C levels. The decision to give alpelisib should consider the inclusion/exclusion criteria in the study Solar-1.
• Patients receiving alpelisib with ET for PIK3CA-mutated ABC should take non-sedating antihistamines to prevent rash. These can be discontinued after 4 weeks, as the risk for rash is primarily in the first two weeks of therapy.

• Options include single agents not previously used (steroidal and non-steroidal AIs, tamoxifen, fulvestrant, megesterol acetate, low dose oestrogen), and potentially abemaciclib.
• Challenging a patient with an agent on which the disease previously progressed, after an initial response, can be occasionally considered.

• Neratinib + capecitabine is not recommended for routine clinical practice.
• Trastuzumab deruxtecan is an option in heavily pretreated patients. Pulmonary toxicity can be fatal and requires active surveillance and proper management.
• Dual blockade with tucatinib + trastuzumab + capecitabine, if approved, can be considered an option for patients previously treated with trastuzumab, pertuzumab and T-DM1, including patients with brain metastases.
• Margetuximab + chemotherapy is not recommended for routine clinical practice.

• Atezolizumab + nab-paclitaxel is an option for first-line therapy for PD-L1+ triple negative ABC, either de novo or ≥12 months since (neo)adjuvant chemotherapy.
• Checkpoint inhibitor monotherapy in later lines is not recommended.

• Mature OS data are needed before Veliparib can be recommended for routine clinical practice.

PIK3CA mutation status

• If treatment with Pi3k inhibitor alpelisib is available, patients should be tested for PIK3CA mutation (in exon 9 and 20) in a tissue (metastasis or primary) and/or in ctDNA testing in blood.
• Tumour biopsy for PIK3CA mutation testing can be considered.

• ESR1 mutation status assessment is not recommended for demonstration of disease progression or selection of endocrine treatment.

PD-L1 status

• PD-L1 status should be tested in cases of first-line triple negative ABC, if treatment with immune checkpoint inhibitors is available.

• Patients with low (1-10%) ER (and PR) positive, HER2 negative ABC should not be considered for endocrine therapy exclusively.