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Dr. Natasha Leighl now reviews data from the PALOMA-3 Trial at #ASCO24 Very excited to hear about this data regarding subcutaneous amivantamab-- a real potential to transform the...
#ASCO24 PALOMA-3 trial: SC amivantamab vs IV amivantamab (both in combination with lazertinib) 💥SC ami demonstrated noninferior PK and ORR compared to IV 📌 PFS and OS➡️longer in the...
Some #LBAs already out! ➡️ PALOMA-3 (NCT05388669): SC amivantamab (ami) + lazertinib (laz) vs IV ami + laz in EGFR-mutated advanced NSCLC. 📊 Results: - Noninferior PK &...
#lungcancer RCT of Subcutaneous versus I.V. Amivantamab (EGFR bispecific) in PALOMA-3 presented by Dr Leigh’s #ASCO24. Non-inferior for safety, efficacy + intriguing...
Can’t wait to hear more about PALOMA-3 TODAY at #ASCO24 Subcutaneous Amivantamab has the potential to ⬇️ infusion-related reactions & clinic visits/time that patients have...
$JNJ flies towards a more convenient Rybrevant, but has a long way to go before this is a $5bn product #ASCO24 via @ApexOnco
Can’t wait to hear more about PALOMA-3 TODAY at #ASCO24 Subcutaneous Amivantamab has the potential to ⬇️ infusion-related reactions & clinic visits/time that patients have...
PALOMA-3 trial: SC vs. IV amivantamab + lazertinib in EGFR-mutant NSCLC. Similar ORRs, numerically better PFS, improved OS with SC vs. IV. Significant reduction in IRRs with SC vs. IV (shorter...
Compelling data presented today from the PALOMA-3 trial (amivantamab) in EFGR mutant NSCLC #LCSM SC administration wins over IV and reduces burden on patients by reducing adelverse...
PALOMA-3 SubQ vs I. Ami+lazer in post osi, post chemo setting (Dr Leighl). PK non-inferiority endpoints met. ORR non inferior. DOR and PFS and OS (sign) improved for SC. TRAEs similar between arms....
PALOMA-3 is the pivotal Phase III, randomized, double-blind, placebo-controlled trial that established palbociclib (Ibrance) plus fulvestrant as a standard of care for women with HR+/HER2- advanced or metastatic breast cancer whose disease progressed on prior endocrine therapy. The trial enrolled 521 women regardless of menopausal status and demonstrated a clinically meaningful and statistically significant PFS benefit that has been supported by over 6 years of follow-up data including ctDNA biomarker analyses.
Phase III, international, multicenter, 2:1 randomized, double-blind, placebo-controlled trial (NCT01942135). Patients received palbociclib 125 mg daily (3 weeks on, 1 week off) plus fulvestrant 500 mg IM, or matching placebo plus fulvestrant. Pre- and perimenopausal women also received concurrent goserelin (LHRH agonist). Stratified by sensitivity to prior hormonal therapy, menopausal status, and presence of visceral metastases.
Women of any menopausal status with HR+/HER2- advanced or metastatic breast cancer whose disease progressed on or after prior endocrine therapy. Patients must have had documented disease progression during or after endocrine therapy. Up to one prior line of chemotherapy for advanced disease was permitted. ER-positive and/or PR-positive (1% or greater staining), HER2-negative by IHC or ISH.
Palbociclib 125 mg orally daily for 21 days of every 28-day cycle plus fulvestrant 500 mg IM on Days 1 and 15 of Cycle 1, then every 28 days. Versus matching placebo plus fulvestrant on the same schedule.
Primary endpoint: investigator-assessed PFS (RECIST 1.1). Key secondary endpoints: OS, ORR, DoR, CBR (CR/PR/SD 24 weeks or more), safety, pharmacokinetics, and patient-reported outcomes including time to deterioration in pain.
Palbociclib plus fulvestrant demonstrated a clinically meaningful and statistically significant PFS improvement. At the interim analysis, median PFS was 9.2 months vs. 3.8 months (HR 0.42; 95% CI: 0.32-0.56; p<0.000001). At the final PFS analysis, median PFS was 9.5 months vs. 4.6 months (HR 0.46; 95% CI: 0.36-0.59; p<0.000001). ctDNA analyses showed PFS benefit regardless of ESR1 (HR 0.25 for ESR1-mutated), PIK3CA, or TP53 mutation status.
With extended follow-up of 73.3 months, palbociclib plus fulvestrant maintained a clinically meaningful OS benefit. Median OS was 34.8 months (95% CI: 28.8-39.9) vs. 28.0 months (95% CI: 23.5-33.8) (stratified HR 0.81; 95% CI: 0.65-0.99). 5-year OS rate: 23.3% vs. 16.7%. 6-year OS rate: 19.1% vs. 12.9%. In patients without prior chemotherapy for ABC, median OS was 39.3 months vs. 29.7 months (HR 0.72; 95% CI: 0.55-0.94). The earlier protocol-specified final OS analysis (median follow-up 44.8 months) showed median OS of 34.9 vs. 28.0 months (HR 0.81; 95% CI: 0.64-1.03; p=0.0429), which did not reach the prespecified significance threshold. Patients with ESR1 mutations showed OS HR 0.59 (95% CI: 0.37-0.94).
The safety profile was generally tolerable with adverse reactions manageable through dose modifications. Neutropenia was the most common AE: 83% all-grade (Grade 3: 55%, Grade 4: 11%). Febrile neutropenia was rare (0.9-1.8%). Other common AEs: leukopenia 53%, infections 47%, fatigue 41%, nausea 34%, anemia 30%, stomatitis 28%. Permanent discontinuation due to AEs: 6% (palbociclib) vs. 3% (placebo). One death from neutropenic sepsis was recorded. QoL was maintained or improved; median time to deterioration in pain was 8.0 months vs. 2.8 months (HR 0.642; p<0.001).
PALOMA-3 established palbociclib plus fulvestrant as a standard of care for HR+/HER2- mBC after prior endocrine therapy. The extended 6-year follow-up confirmed a clinically meaningful OS benefit, particularly in patients without prior chemotherapy and those with endocrine-sensitive disease. The ctDNA biomarker analyses revealed that ESR1-mutated patients derive the greatest benefit (PFS HR 0.25, OS HR 0.59), suggesting a potential role for liquid biopsy-guided treatment selection. Key debate: while no OS benefit was formally significant at the protocol-specified analysis, the consistent trend with extended follow-up and the OS benefit in the no-prior-chemotherapy subgroup support CDK4/6 inhibitor therapy in this setting.