Abemaciclib plus Fulvestrant vs Fulvestrant Alone for HR+, HER2- advanced Breast Cancer Following Progression on a Prior CDK4/6 Inhibitor Plus Endocrine Therapy: Primary Outcome of the Phase 3 postMONARCH Trial.
Background
The combination of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard first line treatment for HR+, HER2- advanced breast cancer (ABC).
While disease progression occurs in nearly all patients (pts) with ABC, the optimal treatment for pts who experience progression on a CDK4/6i + ET remains uncertain.
Real-world evidence suggests that use of abemaciclib after disease progression on a prior CDK4/6i prolongs progression-free survival (PFS) in ABC; however, Phase 2 trials with other CDK4/6i have generated mixed results.
Aim
This study presents the primary outcome analysis for the Phase 3 postMONARCH trial (NCT05169567) of fulvestrant + abemaciclib or placebo in pts with HR+, HER2- ABC following disease progression on prior CDK4/6i + ET.
Methods
postMONARCH was a global, double-blind, placebo-controlled study with pts randomized 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant.
Eligible pts had disease progression on a CDK4/6i + AI as initial therapy for ABC or relapse on/after a CDK4/6i + ET as adjuvant therapy for early breast cancer.
No other prior treatment for ABC was permitted. Primary endpoint was investigator-assessed PFS; secondary endpoints included PFS by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety.
Assuming a hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib, with a cumulative 2-sided type I error of 0.05. Kaplan-Meier method was used to estimate PFS curves and treatment effect was estimated using a stratified Cox proportional hazard model
Results
- A total of 368 pts was randomized to abemaciclib + fulvestrant (n = 182) or placebo + fulvestrant (n= 186).
- Most pts (99%) enrolled directly after CDK4/6i + ET as initial therapy for ABC. Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib.
- At interim analysis, the study reached the pre-specified criteria for significantly improved investigator-assessed PFS with abemaciclib + fulvestrant compared to placebo + fulvestrant (169 events, HR = 0.66; 95% CI 0.48 – 0.91; p = 0.01).
- At primary analysis (258 events), the HR was 0.73 (95% CI 0.57 – 0.95), with PFS rates at 6 months of 50% vs 37% for the abemaciclib and placebo arms, respectively.
- Consistent effect was seen across major clinical and genomic subgroups, including pts with baseline ESR1 or PIK3CA mutations. ORR was improved with abemaciclib compared to placebo (17% vs 7%, respectively, in pts with measurable disease).
- PFS according to BICR was also improved with HR = 0.55 (95% CI 0.39 - 0.77). OS remains immature (20.9% event rate). Safety was consistent with the known profile of abemaciclib.
Conclusion
Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy
Reference
Kevin Kalinsky et al., Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.JCO 42, LBA1001-LBA1001(2024).
Trastuzumab Deruxtecan (T-DXd) vs Physician’s Choice of Chemotherapy (TPC) in Patients (pts) with Hormone Receptor-positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-low or HER2-ultralow Metastatic Breast Cancer (mBC) with Prior Endocrine Therapy (ET): Primary Results from DESTINY-Breast06 (DB-06).
Background
T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT).
Aim
DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC.
Methods
Pts with HER2-low or -ultralow, HR+ mBC were randomized 1:1 to T-DXd 5.4 mg/kg or TPC. Pts had no prior CT for mBC, with ≥2 lines of ET for mBC, or 1 line of ET for mBC if PD occurred ≤24 months (mo) of adjuvant ET or ≤6 mo of ET+CDK4/6i for mBC. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in HER2-low. Key secondary endpoints were PFS in intent-to-treat (ITT = HER2-low and -ultralow) and overall survival (OS). Other endpoints included objective response rate (ORR) and safety.
Results
As of Mar 18, 2024, 866 pts (HER2-low, n=713; HER2-ultralow, n=153) were randomized; 90.4% had prior CDK4/6i. TPC group pts were selected for capecitabine (59.8%), nab-paclitaxel (24.4%) or paclitaxel (15.8%). T-DXd significantly improved PFS vs TPC in HER2-low (HR, 0.62 [95% CI 0.51, 0.74], P<0.0001; median, 13.2 vs 8.1 mo). ITT and HER2-ultralow results were consistent with HER2-low (Table). Median treatment duration was 11.0 mo (T-DXd) vs 5.6 mo (TPC). OS was immature at first interim analysis (HER2-low HR, 0.83 [95% CI 0.66, 1.05], P=0.1181; median follow up, 18.6 mo). Grade (Gr) ≥3 drug-related adverse events occurred in 40.6% (T-DXd) vs 31.4% (TPC). Adjudicated interstitial lung disease / pneumonitis occurred in 49 (11.3%; 0.7% Gr 3/4, 0.7% Gr 5) vs 1 (0.2% Gr 2) pts receiving T-DXd vs TPC.
Conclusion
T-DXd showed a statistically significant and clinically meaningful PFS benefit vs TPC (CT) in HER2-low mBC. HER2-ultralow results were consistent with HER2-low. Safety was in line with known profiles. DB-06 establishes T-DXd as a standard of care following ≥1 endocrine-based therapy for pts with HER2-low and -ultralow, HR+ mBC.
|
|
T-DXd, |
TPC, |
T-DXd, |
TPC, |
T-DXd, |
TPC, |
|
mPFS |
13.2 |
8.1 |
13.2 |
8.1 |
13.2 |
8.3 |
|
PFS HR |
0.62 |
– |
0.63 |
– |
0.78 |
– |
|
12-mo |
87.6 |
81.7 |
87.0 |
81.1 |
84.0 |
78.7 |
|
OS HR |
0.83 |
– |
0.81 |
– |
0.75 |
– |
|
Confirmed |
56.5 |
32.2 |
57.3 |
31.2 |
61.8 |
26.3 |
*HER2-low status investigator assigned;
†subgroup analysis; HER2-ultralow status centrally confirmed;
¤by BICR;
§data immature.
Reference
Giuseppe Curigliano et al., Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). JCO 42, LBA1000-LBA1000(2024).
A-BRAVE Trial: A Phase III Randomized Trial with Avelumab in Early Triple-negative Breast Cancer with Residual Disease After Neoadjuvant Chemotherapy or at High Risk After Primary Surgery and Adjuvant Chemotherapy.
Background
Prognosis of pts with early triple negative breast cancer (TNBC) is still poor and new effective treatments are needed. TNBC is the most immunogenic BC subtype, and this may account for sensitivity to immune checkpoint inhibitors.
Aim
The A-BRAVE trial was designed to evaluate the efficacy of avelumab, an anti PD-L1 antibody, as adjuvant treatment for pts with early TNBC at high risk.
Method
This is a phase III, multicentric, randomized adjuvant study comparing 1 year of treatment with the anti PD-L1 avelumab vs observation for TNBC pts considered at high risk of relapse.
Pts were enrolled after they completed standard treatment with curative intent including surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as: 1) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (Stratum A), 2) >pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum B).
Pts were randomly assigned (1:1, balanced for strata A and B) to Avelumab 10 mg/kg I.V. q2w for 1 year or observation.
Co-primary endpoints were disease free survival (DFS) in the total population and in Stratum A.
474 pts were needed to detect, in the total population, an improvement from 60% to 73.6% 3-year DFS rate (HR 0.6; 90% power, 1-sided test, alfa 2%).
172 DFS events were required to perform the event-driven analysis.
Assuming a proportion of 70-80% pts enrolled in Stratum A, the expected power to detect an HR 0.6 at alpha allocated in this subgroup is 70-79%.
Overall survival was a secondary endpoint.
Results
- From June 2016 to October 2020, 477 pts were randomly assigned from 64 Italian and 6 UK centers. 11 pts (3 avelumab, 8 control) withdrew consent immediately after randomisation and are excluded from further analyses.
- 378 pts entered Stratum A (83%), of whom 99 (57 avelumab, 42 control) received further chemotherapy after surgery prior to enrollment in the trial.
- Efficacy results for the two co-primary DFS endpoints and the secondary OS endpoints are reported in the table.
Conclusion
One year adjuvant avelumab versus control does not significantly improve DFS in high-risk TNBC patients. Nevertheless, the secondary endpoint OS was significantly improved with avelumab vs control. RFS and DMFS will also be reported. A centralized collection of tumor tissue, plasma and feces has been performed and will allow a number of correlative studies.
|
|
Avelumab |
Control |
HR (95% CI) |
p |
|
|
3-year survival % (95% CI) |
3-year survival % (95% CI) |
|
|
|
DFS |
|
|
|
|
|
Total population |
68.3 (61.9-73.8) |
63.4% (56.8-69.3) |
0.82 (0.61-1.11) |
0.193 |
|
Stratum A (post-neoadjuvant) |
66.9 (59.8-73.1) |
61.0 (53.6-67.6) |
0.81 (0.58-1.11) |
0.194 |
|
OS |
|
|
|
|
|
Total population |
85.2 (79.9-89.2) |
78.2 (72.2-83.1) |
0.66 (0.44-0.98) |
0.041 |
|
Stratum A (post-neoadjuvant) |
83.1 (77.1-87.8) |
76.6 (69.6-82.1) |
0.67 (0.44-1.03) |
0.06 |
Reference
Pier Franco Conte et al., A-BRAVE trial: A phase III randomized trial with avelumab in early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk after primary surgery and adjuvant chemotherapy. JCO 42, LBA500-LBA500(2024).
Use of Surgery for De Novo Metastatic Breast Cancer (mBC).
Background
In the U.S., locoregional surgery for de novo mBC was common in the 1990s and 2000s, but subsequent prospective data did not show a survival advantage. Current guidelines recommend surgery only for symptom control.
Aim
This study investigates the use of surgery (lumpectomy or mastectomy) for mBC from 2010 to 2019 using SEER and institutional data, aiming to identify factors that correlate with variability in surgery use
Method
We included all de novo mBC diagnoses from SEER-17 from 2010-2019. The primary outcome was receipt of surgery, and we included year of diagnosis, demographic (race/ethnicity, age, marital status, median household income in the patient’s county, and urban/rural residence), and disease factors (estrogen receptor (ER) and HER2 status, tumor size, and presence of visceral metastases) in the multivariable logistic regression.
We similarly identified all de novo mBC diagnoses from Oncoshare, which merges EMR and California Cancer Registry (CCR) data for patients treated in the Stanford Health Care Alliance.
For Oncoshare inclusion a patient must have an encounter with Stanford and be in CCR; however, a patient does not have to receive all cancer care at Stanford.
In this analysis, we included distance to the cancer center and insurance status. Results are presented as unadjusted percentages or odds ratios with 95% confidence intervals.
Results
- In SEER (n = 24,146), the use of surgery for mBC declined from 41% in 2010 to 22% in 2019, a trend also observed in the institutional data (n = 785).
- Surgery rates were highest in younger patients and declined with each decade of life (44% for those in their 30s vs 19% for those > 80).
- Surgery was more common in tumors > 2 cm, ER-negative disease, and in patients without visceral metastases. In SEER, patients from counties with median incomes < $50,000 were more likely to have surgery than those from counties with incomes > $75,000 (36% vs 27%; OR: 1.3 [1.2-1.5]).
- Rural patients were more likely to have surgery than urban patients (34% vs 30%; OR: 1.1 [1.0-1.3]).
- Unmarried persons had lower odds of surgery than married persons (OR: 0.8 [0.7-0.9]).
- The institutional data reproduced the findings of the SEER analysis, except that a relationship between surgery and marital status and income was not observed.
- In the institutional data, patients living farther from the Stanford Cancer Center ( > 100 km) were more likely to have surgery (40% vs 32%; OR 2.1 [1.2-3.8]).
Conclusion
The use of surgery for de novo mBC decreased dramatically in the 2010s from 41% to 22%. All demographics saw a reduction; however, younger and married patients underwent surgery at higher rates. Patients from lower-income and rural counties—areas typically with less access to care—were also more likely to have surgery. The institutional analysis showed that a greater distance from an urban hospital network correlated with increased odds of surgery. These patterns suggest differential care provision in rural areas for patients with mBC.
Reference
James Dickerson et al., Use of surgery for de novo metastatic breast cancer (mBC).JCO 42, 1590-1590(2024).
First-line Inavolisib/Placebo + Palbociclib + Fulvestrant (Inavo/Pbo+Palbo+Fulv) in Patients (pts) with PIK3CA-mutated, Hormone Receptor-positive, HER2‑negative Locally Advanced/Metastatic Breast Cancer Who Relapsed During/within 12 months (mo) of Adjuvant Endocrine Therapy Completion: INAVO120 Phase III Randomized Trial Additional Analyses
Background
INAVO120 (NCT04191499) showed significantly and meaningfully improved investigator-assessed progression-free survival (PFS; stratified hazard ratio 0.43) with Inavo+Palbo+Fulv v Pbo+Palbo+Fulv, and manageable safety and tolerability.
Aim
This study further characterize the substantial benefit/risk of the Inavo triplet, we assessed additional clinically relevant efficacy endpoints, detailed safety data of key adverse events (AEs) for Inavo (hyperglycemia [HG], diarrhea, rash, stomatitis), and pt-reported outcomes (PROs).
Method
Efficacy endpoints includedtime from randomization to end of next-line treatment (tx; proxy for PFS2) and to first chemotherapy (TTFC). Key AEs were reported by grouped terms. PROs were assessed by PRO-CTCAE, an overall bother item, BPI-SF, and EORTC QLQ-C30.
Results
- Increases in median “PFS2” (24.0 v 15.1 mo; unstratified hazard ratio: 0.59 [95% CI, 0.42–0.83]) and TTFC (NE v 15.0 mo; unstratified hazard ratio: 0.53 [95% CI, 0.37–0.78]) were observed in the Inavo v Pbo arm (median follow-up: 21.3 mo; Table).
- Key AEs were mostly G1–2 and had resolved (Table). No key AEs were G4–5. In the Inavo arm, among pts who experienced key AEs (HG, diarrhea, rash, stomatitis), median time to first onset was 7, 15, 29, and 13 days, respectively.
- The key AEs were managed with standard supportive care and Inavo dose interruptions/reductions. One pt discontinued Inavo due to HG; one, due to stomatitis. Pts receiving Inavo experienced a longer duration of time without worsening pain severity and maintained their day-to-day functioning and health-related quality of life on tx.
- Most pts in both arms reported levels of selected symptomatic AEs from the PRO-CTCAE and overall tx bother as moderate or less, indicating that Inavo does not contribute additional tx burden.
Conclusion
Inavo+Palbo+Fulv was associated with sustained benefit beyond disease progression, delaying chemotherapy administration, with manageable safety and tolerability that was reflected in PROs; hence, supporting it as a new standard of care.
Full Analysis Set
Inavo Arm
n = 161Pbo Arm
n = 164“PFS2” (95% CI), mo
24.0 (18.6–NE)
15.1 (13.5–22.3)
TTFC (95% CI), mo
NE (24.8–NE)
15.0 (10.6–24.8)
Safety analysis set
Pts with ≥1 key AE, n (%)n = 162
n = 162
HG
Any grade
G1–2
G3
Resolved event
95 (59)
86 (53)
9 (6)
75 (46)
14 (9)
14 (9)
0
13 (8)Diarrhea
Any grade
G1–2
G3
Resolved event
78 (48)
72 (44)
6 (4)
68 (42)
26 (16)
26 (16)
0
24 (15)Rash
Any grade
G1–2
Resolved event
41 (25)
41 (25)
35 (22)
28 (17)
28 (17)
25 (15)Stomatitis
Any grade
G1–2
G3
Resolved event
83 (51)
74 (46)
9 (6)
68 (42)
43 (27)
43 (27)
0
38 (23)Reference
Dejan Juric et al., First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses.. JCO 42, 1003-1003(2024).
Trastuzumab and Pertuzumab in Combination with Eribulin Mesylate or a Taxane as First-line Chemotherapeutic Treatment for HER2-positive, Locally Advanced or Metastatic Breast Cancer: Results of a Multicenter, Randomized, Non-inferiority Phase 3 Trial in Japan (JBCRG-M06/EMERALD).
Background
Trastuzumab (H) + pertuzumab (P) + taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2–positive (HER2+) breast cancer (BC). However, taxane-induced toxicities, which reduce patient quality of life (QoL), necessitate development of less toxic but at least equally effective taxane alternatives.
Aim
This study investigated the non-inferiority of eribulin to taxane when used in combination with dual HER2 blockade (HP).
Method
The multicenter randomized open-label parallel-group phase 3 EMERALD trial (UMIN000027938, NCT03264547) was carried out to test the non-inferiority of eribulin + HP (study regimen) against docetaxel/paclitaxel + HP (control regimen) as first-line chemotherapeutic treatment in patients with locally advanced or metastatic HER2+ BC. The study design has been published (doi: 10.1186/s13063-020-04341-y).
Patients were randomized (1:1) to receive, by intravenous infusion in a 21-day cycle, either (i) eribulin 1.4 mg/m2 on days 1 and 8, or (ii) a taxane (docetaxel 75 mg/m2 on day 1 or paclitaxel 80 mg/m2 on days 1, 8 and 15), each being administered in combination with HP on day 1.
The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, overall survival (OS), QoL and safety.
Non-inferiority was tested using the Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events.
The upper limit of acceptance of non-inferiority HR margins (1.33 and 1.25) was tested in a stepwise manner.
Results
- Between August 2017 and June 2021, 446 patients (224 and 222 in the study and control groups, respectively) were enrolled: median age was 56.0 (29–70) years, 244 (54.7%) had ER-positive BC, 285 (63.9%) had visceral metastasis.
- While 247 patients (55.4%) had de novostage 4 disease, 199 (44.6%) underwent radical surgery and 138 (30.9%) received taxanes perioperatively. Both groups’ baseline characteristics were well balanced.
- Median PFS was 14.0 mos in the study group and 12.9 mos in the control group (HR, 0.96; 95% CI, 0.77–1.20), confirming non-inferiority of the study regimen. Median OS was 65.3 mos in the control group but has not been reached in the study group.
- Incidences of adverse drug reactions including grade ≥3 febrile neutropenia, edema and diarrhea were numerically lower in the study group than in the control group (4.9% vs 8.7%, 8.5% vs 42.2% and 36.6% vs 54.1%, respectively).
Conclusion
This is the first study to show non-inferiority of eribulin to taxane when used in combination with dual HER2 blockade. As a less toxic but equally effective alternative to the taxane-containing regimen, eribulin combined with HP could be first-line treatment of locally advanced or metastatic HER2+ BC.
Reference
Toshinari Yamashita et al., Trastuzumab and pertuzumab in combination with eribulin mesylate or a taxane as first-line chemotherapeutic treatment for HER2-positive, locally advanced or metastatic breast cancer: Results of a multicenter, randomized, non-inferiority phase 3 trial in Japan (JBCRG-M06/EMERALD).. JCO 42, 1007-1007(2024).
Overall Survival with Palbociclib (PAL) plus an Aromatase Inhibitor (AI) versus AI Alone in Older Patients (pts) with De Novo, HR+/HER2− metastatic Breast Cancer: A SEER-Medicare Analysis.
Background
Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts.
Aim
This study primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset.
Method
We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included.
Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first.
Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses.
Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively.
Results
- Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91).
- Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table).
Conclusion
This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population.
|
|
Unadjusted |
Unadjusted |
After sIPTW |
After sIPTW |
|
Variable |
PAL + AI (N=296) |
AI Alone (N=483) |
PAL + AI (N=296) |
AI Alone (N=482) |
|
Age Group (%): 65-69 years |
29.1 |
17.8 |
22.5 |
22.2 |
|
70-74 years |
28.4 |
18.8 |
22.2 |
22.0 |
|
75-79 years |
22.6 |
20.9 |
21.6 |
21.7 |
|
≥ 80 years |
19.9 |
42.4 |
33.7 |
34.1 |
|
Bone disease (%) |
78.7 |
73.5 |
75.8 |
75.9 |
|
Liver metastases (%) |
13.5 |
13.5 |
14.4 |
13.8 |
|
Lung metastases (%) |
26.4 |
29.6 |
27.4 |
28.0 |
|
NCI Comorbidity Index Score >1 (%) |
10.5 |
19.7 |
16.8 |
16.3 |
Reference
Adam Brufsky et al., Overall survival with palbociclib (PAL) plus an aromatase inhibitor (AI) versus AI alone in older patients (pts) with de novo, HR+/HER2− metastatic breast cancer: A SEER-Medicare analysis.. JCO 42, 1111-1111(2024).
Outcome with Pertuzumab, Docetaxel, and Trastuzumab (PTH) Regimen in Patients with HER2 Positive Metastatic Breast Cancer: Real-world Data from a Single Center in India.
Background
Pertuzumab, Docetaxel and Trastuzumab (PTH) regimen constitutes one of the standard treatment regimens in human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC).
Aim
This real-world outcomes of its use from the Indian sub-continent are lacking so this study focus on outcomes of PTH in HER+ MBC patients.
Method
We retrospectively reviewed the medical records of HER2-positive MBC treated with an upfront PTH regimen at the All India Institute of Medical Sciences, New Delhi, India, between Aug 2016 to July 2023.
A total of six cycles of PTH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were planned along with granulocyte-colony stimulating factor (GCSF) prophylaxis.
Patients were continued on maintenance trastuzumab after 6 cycles (till disease progression) and hormonal agent if indicated.
The primary outcome was progression-free survival (PFS). The secondary outcome was overall survival (OS), overall response rate (ORR) rates, and toxicity.
Results
- Eighty-seven were included with a median age of 48 years (range, 25-73). Overall, 38 (43.6%) patients had hormone-positive (estrogen receptor and or progesterone receptor) disease and 48 (55.17%) were premenopausal.
- Thirty-five (40.2%) patients had received prior adjuvant and neoadjuvant treatment. Eighty patients (91.5%) had visceral metastasis and the most common site was the liver followed by the lung.
- After a median follow-up of 36 months, the median PFS was 15 months and OS was 42 months.
- The ORR was 85.3% and complete response (CR) was observed in 14(16.09%) patients. The survival outcomes were significantly better among those with hormone-negative disease and among those who achieved CR after 6 cycles of PTH.
- Grade 3/4 toxicity was seen in 12% of patients which led to dose modification, interruption, and change in chemotherapy.
- Two patients developed reversible left asymptomatic ventricular systolic dysfunction. None of the patients developed congestive heart failure.
- The most common grade 3/4 toxicities were diarrhea in 8 (9.1%) patients, cutaneous rash in 2 (2.2%) patients and thrombocytopenia in 2 (2.2%) patients. There were two cases of febrile neutropenia.
Conclusion
In a real-world context, PTH is an effective and well-tolerated regimen for in patients with HER2-positive MBC in India. Hormone-positive disease has poor survival compared with hormone negative disease.
Reference
Ajay Gogia et al., Outcome with pertuzumab, docetaxel, and trastuzumab (PTH) regimen in patients with HER2 positive metastatic breast cancer: Real-world data from a single center in India.JCO 42, e13037-e13037(2024).
Neoadjuvant Pertuzumab, Docetaxel, Carboplatin, and Trastuzumab (PTCH) Regimen in Patients with HER2 Positive Early, Locally Advanced, and Oligometastatic Breast Cancer: Real-world Indian Experience.
Background
Pertuzumab/docetaxel/carboplatin/trastuzumab (PTCH) regimen constitutes one of the standard neoadjuvant treatments in human epidermal growth factor receptor-2 (HER2) positive breast cancer.
Aim
The real-world outcomes of its use from the Indian sub-continent are lacking so this study focus on PTCH combination in early HER2+ Breast cancer.
Method
We retrospectively reviewed the medical records of 114 HER2-positive BC patients presenting with nonmetastatic or oligometastatic disease and treated with a uniform PTCH regimen in a neoadjuvant setting at the All India Institute of Medical Sciences, New Delhi, India, between Jan 2015 to May 2023.
Total six cycles of PTCH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), carboplatin (AUC 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were administered with primary GCSF prophylaxis.
The primary outcome was invasive disease-free survival (iDFS). The secondary outcomes included pathological complete response (pCR) rates, overall survival (OS), and toxicity.
Adjuvant trastuzumab is used for patients achieving pCR, while for patients not achieving pCR option of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab was decided based on patient affordability.
Results
One hundred and fourteen (114) patients were included with a median age of 47 years (range, 23-70). Overall, 52 (45.6%) patients had hormone-positive disease and 73 (64.01%) were premenopausal.
Forty patients (35.08%) had stage II, 62 (54.38%) had stage III, and 12(10.5%) had oligometastatic disease.
Sixty-one (53.5%) patients underwent breast conservation surgery and pCR was observed in 62 (54.38%) cases.
With a median follow-up of 31 months, the 3-year iDFS was 81.5% and overall OS was not reached. Median iDFS was 33 months in patients with node-positive disease and was not reached in patients with node-negative disease.
Three-year iDFS was 68.1% in patients who achieved pCR and 49.8% in those who did not achieve pCR (p=0.001).
Grade 3/4 toxicity was seen in 26.7% of patients which caused dose modification and interruption in 13.9% of patients.
The most common grade 3/4 toxicity was diarrhea in16 (14.03%) cases and thrombocytopenia in 11 (9.6)% cases .
Febrile neutropenia was seen in 4 (3.5%) patients. Four patients (3.5%) had a reversible decrease in cardiac left ventricular ejection fraction.
Conclusion
In a real-world context, PTCH is an effective and safe anthracycline-free regimen for use in curative (adjuvant and neoadjuvant) setting for HER2 positive breast cancer in Indian women Using neoadjuvant PTCH may improve pCR and obviate the need for adjuvant T-DM1 after surgery making it a cost-effective strategy in limited recourse setting. The survival outcomes were significantly better among those with node-negative disease and among those who achieved a pCR.
Reference
Ajay Gogia et al., Neoadjuvant pertuzumab, docetaxel, carboplatin, and trastuzumab (PTCH) regimen in patients with HER2 positive early, locally advanced, and oligometastatic breast cancer: Real-world Indian experience. JCO 42, e12556-e12556(2024).
