LBA12 PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer

Mayer, Erica L.; Gnant, Michael; DeMichele, Angela; Martín, Miguel; Burstein, Harold J.; Prat, Aleix; Rubovszky, Gábor; Miller, Kathy D.; Winer, Eric P.; Zdenkowski, Nicholas; Anderson, D. Mark; Nowecki, Zbigniew; Loibl, Sibylle; Fohler, Hannes; Metzger, Otto; Fumagalli, Debora; Theall, Kathy Puyana; Fesl, Christian; Dueck, Amylou C.

doi:10.1016/j.annonc.2020.08.2240

Cited by 30 publications

(36 citation statements)

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“…All studies were phase III trials. Two studies (PALLAS and PENELOPE-B) evaluated the addition of the CDK4/6i palbociclib to ET, 9,10 and one (monarchE) the addition of abemaciclib. 11,12 The duration of the adjuvant therapy with CDK4/6is was 2 years in the PALLAS and monarchE trials, and 1 year in the PENELOPE-B trial.…”

Section: Resultsmentioning

confidence: 99%

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

et al. 2021

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Background: The combination of cyclin-dependent kinases 4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is standard of care for patients with hormone receptor-positive (HRþ), HER2-negative (HER2À) advanced breast cancer (BC). However, studies evaluating adjuvant CDK4/6is provided contradictory results thus far. Materials and methods: We conducted a systematic review and meta-analysis to assess if the addition of CDK4/6is to adjuvant ET impacts on survival's outcomes and safety of patients with HRþ/HER2À early BC (EBC). This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and was registered in the PROSPERO database (ID: CRD42020218597). A systematic review of PubMed, Cochrane and EMBASE databases and major conference proceedings was performed up to 15 December 2020. All randomized controlled trials including patients with HRþ/HER2À EBC treated with CDK4/6is plus ET versus ET alone in the adjuvant setting were included. Pooled hazard ratios (HRs) and odds ratios (ORs) for survival and safety outcomes, respectively, were calculated with 95% confidence intervals (95% CIs) using random effect models. Results: With data available from three studies (N ¼ 12 647), the addition of CDK4/6is to adjuvant ET showed a trend for a benefit in terms of invasive disease-free survival (IDFS; HR 0.85, 95% CI 0.71-1.01; P ¼ 0.071). No significant improvement in distant relapse-free survival was observed (HR 0.83, 95% CI 0.58-1.19; P ¼ 0.311). The risk of allgrade toxicities and early treatment discontinuation increased significantly with the addition of CDK4/6is to ET (OR 9.36, 95% CI 3.46-25.33, P < 0.001, and OR 22.11, 95% CI 9.45-51.69, P < 0.001, respectively). Conclusion: The administration of adjuvant CDK4/6is to patients with HRþ/HER2À EBC showed a trend for an IDFS benefit and an increase in the risk of toxicities and treatment discontinuation. The role of adjuvant CDK4/6is remains controversial and a longer follow-up of these randomized controlled trials is needed before supporting a straightforward change in clinical practice.

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Section: Resultsmentioning

confidence: 99%

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

et al. 2021

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“…Another open-label, phase III study evaluating CDK4-6i in the adjuvant setting, the PALLAS trial, randomly assigned 5760 stage II–III HR+/HER2− EBC patients to receive standard adjuvant ET with or without palbociclib (125 mg once daily on days 1–21, followed by 7 days off) for 2 years. 4 Surprisingly, no improvement in IDFS was observed (HR 0.93, 95% CI 0.76 to 1.15; p=0.51), with these results crossing a futility boundary prespecified in the study statistical assumptions. No specific subgroup appeared to benefit from the addition of palbociclib to ET.…”

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confidence: 80%

“…Most common toxicities in palbociclib arm were haematological (neutropenia, 83% all grades and 61% grade 3–4), followed by fatigue (40% all grades, 2% grade 3–4) and upper respiratory tract infection (28% all grades, 1% grade 3–4). 4 It will be important to understand the impact of CDK4/6i in quality of life, which is still not reported in either trial.…”

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confidence: 99%

CDK4/6 inhibition in HR-positive early breast cancer: are we putting all eggs in one basket?

2020

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“…In particular, MonarchE trial reported a significant advantage of 3.5% in term of invasive DFS in patients who received abemaciclib plus ET compared to those treated with ET alone (92.2% versus 88.7%) ( 80 ). Conversely, in the PALLAS trial, the addition of palbociclib to adjuvant ET did not prolong invasive DFS versus ET alone (88.2% versus 88.5%) ( 81 ). These conflicting results may be due to several differences between the two trials such as study populations (more high-risk patients enrolled in MonarchE trial), drug exposure and follow up duration.…”

Section: Management and Treatment Of Ilcmentioning

confidence: 99%

Lobular Breast Cancer: A Review

et al. 2021

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Invasive lobular carcinoma accounts for 5%–15% of all invasive breast cancers, with a marked increase in incidence rates over the past two decades. Distinctive biological hallmarks of invasive lobular carcinoma include the loss of cell adhesion molecule E-cadherin leading to cells with a discohesive morphology, proliferating into single-file strands and estrogen receptor positivity. These key molecular features can make diagnosis difficult, as invasive lobular carcinoma is challenging to detect both physically and with current standard imaging. Treatment of invasive lobular carcinoma strongly favors endocrine therapy due to low chemosensitivity and lower rates of pathological response as a result. This review will summarize the distinct biological and molecular features of invasive lobular carcinoma, focusing on the diagnostic challenges faced and the subsequent surgical and medical management strategies. Prospective therapeutic options will also be explored, highlighting how furthering our understanding of the unique biology of lobular breast carcinoma is essential in guiding and informing the treatment of patients in the future.

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LBA12 PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer

Cited by 30 publications

References 0 publications

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

CDK4/6 inhibitors as adjuvant treatment for hormone receptor-positive, HER2-negative early breast cancer: a systematic review and meta-analysis

CDK4/6 inhibition in HR-positive early breast cancer: are we putting all eggs in one basket?

Lobular Breast Cancer: A Review

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