First line aromatase inhibitor (AI) + pa l bocicl i b with randomized switch to fulvestrant + palbociclib upon detection of circulating ESR1 mutation in HR+ HER2-metastatic breast cancer patients: Global safety results of PADA-1, a UCBG-GINECO phase III trial
Cancer Research
; 82(4 SUPPL), 2022.
Article
in English
| EMBASE | ID: covidwho-1779449
ABSTRACT
Background:
Aromatase inhibitors (AI) in combination with a CDK 4/6 inhibitor have been established as the standard first line treatment of non AI-resistant hormone receptor-positive (HR+) HER2-metastatic breast cancer (mBC) patients (pts). ESR1 mutations are known drivers of resistance to AIs in the metastatic setting but their actionability remains unknown. The phase 3 PADA-1 trial aimed both at refining the global safety of palbociclib combined to any AI as first line treatment of HR+ HER2-mBC pts, and at evaluating the clinical benefit associated with a switch to fulvestrant-palbociclib upon detection of a rising ESR1 mutation in blood (bESR1mut).Methods:
PADA-1 (NCT03079011), a multicenter, randomized, open-label, phase 3 trial, enrolled HR+ HER2-mBC pts with no prior therapy for mBC, in the absence of AI-resistance. In the first step, pts received a combination of any AI and palbociclib at standard recommended doses and underwent centralized bESR1mut screening every two months. In the second step, bESR1mut+ pts with no S clinical/imaging concomitant disease progression were randomized between continuing the same therapy (standard arm) or switching to fulvestrant-palbociclib (experimental arm). The third step consisted in an optional cross-over after tumor progression for patients randomized in the standard arm. PADA-1 co-primary endpoints were global safety of the combination of palbociclib + endocrine therapy in the whole population of patients, throughout the study, with focus on hematological toxicities;and PFS in the second step. We present here the results of the global safety co-primary endpoint.Results:
From 3/2017 to 01/2019, 1017 pts were accrued in 83 sites. As per 05/2021, 272 pts were still in step 1, 35 in step 2, and 8 in step 3. The overall follow-up was 33.7 months. 232 pts have deceased. 333 SAEs have been reported, including 21 grade 5, 35 grade 4, 183 grade 3, 53 grade 2, 26 grade 1 and 15 unknown grade. Among the grade 5 cases, 2 have been declared as potentially related to the underlying treatment (Death of unknown cause, pulmonary embolism). No pt died of SARS-CoV2 infection. The main hematological toxicities encountered, as well as selected non-hematological events are described in Table 1. Permanent discontinuation of the treatment due to toxicity occurred in 39 pts/1017 (3.8%). Palbociclib dose decreases occurred in 419 (41.2%) pts.Conclusion:
By the number of included patients, PADA-1 is the largest prospective trial with 1st line AI and palbociclib. Data confirm the favorable safety profile of palbociclib when combined to any AI +/-switch to fulvestrant. Hematological toxicity appears limited and is mostly restricted to non-clinically significant neutropenia. Permanent discontinuation was exceptional. Detailed per-step analyses will be presented.
aromatase inhibitor; endogenous compound; epidermal growth factor receptor 2; estrogen receptor alpha; fulvestrant; hormone receptor; palbociclib; adult; blood toxicity; cancer inhibition; cancer patient; clinical evaluation; clinical trial; conference abstract; controlled study; coronavirus disease 2019; drug combination; drug safety; drug therapy; drug withdrawal; female; follow up; gene mutation; genetic susceptibility; hormonal therapy; human; lung embolism; major clinical study; metastatic breast cancer; multicenter study; neutropenia; phase 3 clinical trial; prospective study; randomized controlled trial; tumor growth
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Randomized controlled trials
Language:
English
Journal:
Cancer Research
Year:
2022
Document Type:
Article
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