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PHERGain-2 Trial

Phase III chemotherapy-free, ctDNA-guided trastuzumab + pertuzumab in early HER2+ breast cancer. 59.6% pCR with concurrent Annals of Oncology publication at ESMO Breast 2026.

MEDSIR (investigator-initiated) HER2+ Early Breast Cancer Trastuzumab + Pertuzumab Phase III ESMO Breast 2026 Chemotherapy-Free Concurrent Annals Pub
Explore Trial Data

Top KOLs Discussing PHERGain-2

Paolo Tarantino
Paolo Tarantino
@PTarantinoMD
381 impressions
Erika Hamilton, MD, FASCO
Erika Hamilton, MD, FASCO
@ErikaHamilton9
260 impressions
KOL Pulse AI
KOL Pulse AI
@KolPulseAI
210 impressions
Uur zkerim
Uur zkerim
@UOzkerim
110 impressions
Abi Siva MD
Abi Siva MD
@AbiSivaMD
55 impressions
Angel Guerrero-Zotano, MD,PhD
Angel Guerrero-Zotano, MD,PhD
@AngelZotano
26 impressions
Presenting Author at ESMO Breast 2026 (#ESMOBreast26)
Antonio Llombart Cussac, MD, PhD
Antonio Llombart Cussac, MD, PhD
Hospital Arnau de Vilanova, Valencia, Spain (MEDSIR)
Co-authors: Llombart Cussac A, Bianchini G, Cortés J, Pérez-García JM, et al.

PHERGain-2 Key Slides & Visuals

Trial slides shared by KOLs at ESMO Breast 2026 (#ESMOBreast26). Click any image to expand. OCR text extracted via AWS Textract.

Paolo Tarantino
Paolo Tarantino @PTarantinoMD
PHERGain-2
326 impressions · 8 likes · 2026-05-06
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[Slide 1]
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
PHERGain-2 Study Design
TREATMENT
Key eligibility criteria
Cohort A
pCR
Patients 2 18 years
Histologically confirmed
ypTO/is
HP (±ET)
x10
invasive carcinoma of
ypNO
the breast
Primary Endpoints
No prior treatment for
At screening:
Cohort B
Central
breast cancer
HP (±ET)
HER2 IHC 3+*
x8
Breast MRI
Surgery
ypN0(i+)
HER2 status
T-DM1 (±ET)
(1) >10% HRQoL
ypN0(mol+)
EoS
&
ypN1mi
x10
decline rate
Node-negative status
Tumor size 5-30 mm
MRI imaging
(2) 3y-RFI rate
(MRI)
Cohort C
ECOG PS 0/1
ChT' T-DM1
LVEF >55%
ypN1-N3
(+ET)
Adequate organ function
HP: 600 mg H plus 1200 mg P loading
x10
dose, then 600 mg H plus 600 mg P
Physician's choice chemotherapy was allowed
maintenance dose q3w
before adjuvant T-DM1
T-DM1: 3.6 mg/kg of body weight q3w
ET up to 5 years and radiotherapy as per
Follow-up*
HR status and institutional practices
PROs
assessments: Baseline
D1C1-C8
<14d pre-op
Adj D1C1
FU q3m x2y
FU q6m x3y
Annual to EOS
"According to the 2018 American Society of Clinical Oncology/College of American Pathologists criteria.
TAII patients who were hormonal receptor-positive received ET concomitantly with HP or T-DM1. ET was sex- and menopausal status-based premenopausal and perimenopausal women receive ovanan function suppression plus tamoxifen (20 mg/day
orally) or letrozole (2.5 mg/day orally); postmenopausal women receive letrozole (2.5 mg/day orally): and men receive tamoxifen (20 mg/day orally).
*All patients must be followed up for 5 years from when the last patient has completed surgery (EoS), even if the assigned treatment is discontinued permanently
ChT, chemotherapy, ECOG PS, Eastern Cooperative Oncology Group performance status; d, day, EoS, end of study, ET, endocrine therapy, FU, follow-up; HER2, human epidermal growth factor receptor 2; HP, trastuzumab and pertuzumab; HRQoL. health related quality of
life; IHC, immunohistochemistry, LVEF, left ventricular ejection fraction; m, month; MRI, magnetic resonance imaging pCR pathological complete response; PRO, patient-reported outcomes; RFI, recurrence-free survival; q3w, every three weeks; y. year

---

[Slide 2]
Baseline Characteristics
N = 396
N = 396
Patient baseline characteristics
Primary tumor baseline characteristics
n (%)
n (%)
Age; Median (range) (years)
55 (24-85)
Median tumor size (mm, Min; Max)
18 (7-30)
Sex
T stage1, mm
Woman
394 (99.5)
T1b/T1c: >5 to <20
244 (61.6)
T2: >20 to <30
Menopausal status
152 (38.4)
Postmenopausal
235 (59.3)
Histologic grade
Gx*
57 (14.4)
Premenopausal
159 (40.2)
G1
21 (5.3)
Not available
2 (0.5)
G2
185 (46.7)
ECOG performance status
G3
133 (33.6)
0
382 (96.5)
HER2 IHC 3+
396 (100)
1
14 (3.5)
Hormonal receptor status
Multifocal or multicentric breast cancer
15 (3.8)
Negative
108 (27.3)
ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2;
Positive
288 (72.7)
IHC, immunohistochemistry
Tumor staging was assessed as per American Joint Committee on Cancer staging manual, 8th edition
"Differentiation status could not be assessed
*All patients who were hormonal receptor-positive received ET concomitantly with HP or T-DM1. ET was sex- and menopausal
status-based premenopausal and perimenopausal women receive ovanan function suppression plus tamoxifen (20 mg/day orally)
or letrozole (2.5 mg/day orally); postmenopausal women receive letrozole (25 mg/day orally); and men receive tamoxifen (20
Dr. Antonio Llombart-Cussac
mg/day orally).
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use
n (%), number of patients (percentage based on N); N, Number of patients
ESMO

---

[Slide 3]
Primary safety endpoint: >10% HRQoL decline rate at one
year
≥10% HRQoL decline rate
Patient-reported outcomes
N = 396 ; n (%)
Completion rate at baseline
391 (98.7)
42.8%
95% CI 36.9-48.8
Baseline HRQoL score, mean (95% CI)
78.6 (76.8-8 0.5)
Completion rate at 1 year
360 (90.9)
HR positive: 45.2% (95% CI 38.3-52.3)
Fisher's exact test
1-year HRQoL score, mean (95% CI)
69.6 (67.5-71.8)
HR negative: 36.1% (95% CI 25.4-47.9)
p 0.11
n (%), number of patients (percentage based on N); N, Number of patients.
Patient reported outcomes were analyzed on patients who received at least one dose of study treatment and completed baseline and at least one follow-up questionnaire 1. year post-neoadjuvant treatment
Patients without a >10% decline at one year who discontinued the study due to disease progression, toxicity or death within the first year after starting neoadjuvant treatment were considered events
Dr. Antonio Llombart-Cussac
Content of this presentation is copyright and responsibility of the author Permission is required for re-use
ESMO
CI, confidence interval; HR, hormone receptor, HRQoL, health-related quality of life

---

[Slide 4]
Secondary endpoint: pCR rate by HR status and tumor size
Median (range) T1 tumor size: 16mm (7-20)
Median (range) T2 tumor size: 23.5mm (21-30)
100
pCR rate
100
100
59.6%
63.0%
59.6%
95% CI 54.6-64.4
95% CI 53.1-72.1
95% CI 53.3-65.7
80
80
80
59.6%
58.3%
Pathological complete response (%)
95% CI 51.0-67.7
95% CI 52.4-64.1
60
60
60
40
40
40
236 / 396
68 / 108
168 / 288
152/255
20
84 141
20
20
0
0
0
All participants
HR-
HR+
T1
T2
Fisher's exact test
Fisher's exact test
p=0.42
P 1.00
Dr. Antonio Liombart-Cussac
Content of this presentation is copyright and responsibility of the author Permission is required for re-use.
ESMO
CI, confidence interval; HR, hormone receptor, pCR pathological complete response
Erika Hamilton, MD, FASCO
Erika Hamilton, MD, FASCO @ErikaHamilton9
PHERGain-2
260 impressions · 6 likes · 2026-05-08
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[Slide 1]
2140: pCR-guided strategy with HP & T-DM1 in PHERGain-2
Lombert-Cussac et al
De-escalate therapy for low risk/HER2 strongly +
TREATMENT
N=236
Key eligibility criteria
Cohort A
PCR
59.6% pCR rate (95% CI 54.6-64.4)
Patients 19 yours
ypToM
HP (BET)
Histologically sentemed
N10
investive cancinoma of
N=396
ypMo
Varied by HR status: 63% HR-; 58.3% HR+
the
No proor treatment for
At screening
Central
breast cancet
HP (BET)
HER2 education
Bread
Cohort B
Surgery
Primary Endpoints
No variation in pCR by tumor size
HER2 INC "
*8
ypND(mol+)
T-DM1 (eET)
....
EoS
&
*10
Node-megative status
(1) >10% HRQoL
Tumor size 5-30 mm
MR) maging
decline rate
Greater decline in HRQoL in arm B and C than arm A
(MR)
Cohort c
ECOG DT
Chi T-OM1
(2) 3y-RF rate
LVEF #55%
YPN1-N3 N3
(#ET)
Main toxicity diarrhea and fatigue
Adequate organ function
NP 600 mg M plus 1200 mg P loading
#10
N-7
dose, then 600 mg plus 600 mg P
Physician's child thematheripy - slowed
One death due to pneumonitis with T-DM1
maintenance dose q3w
before adjuvant 1-CM
T-DM1 3.6 mgkg of body weight (3w
ET up 105 years and radiotherapy as per
Folow-up
HR status and institutional practices
PROs
assessments:
Baseline
D1C1-C8
$144 pre-op
Adj D1C1
FU q3m *2y
FU q6m *3y
Annual to EOS
Conclusions
The trial met its primary endpoint of HRQOL
PHERGain-2: pCR-adapted de-escalation with HP and T-DM1 in highly
High pCR rate even though 3/4 of patients had HR+
selected patients with HER2+ IHC 3+, N- EBC
disease
Primary endpoints safety and relapse free interval
Await 3-year RFI
34 pts dropped out after surgery
Median FU: 15.1 months (0.49-36.1); 73% HR+
This data suggests that up to 60% of patients with
CS with CamScanner
Scanned 5. Rugo, MD
node negative strongly HER2+ EBC could potentially
be cured with antibody therapy alone
Content of this presentation is copyright and responsibility of the author Permission is required for re-use
ESMO
KOL Pulse AI
KOL Pulse AI @KolPulseAI
PHERGain-2
210 impressions · 2 likes · 2026-05-07
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[Slide 1]
KOL Pulse / Conference
Intelligence
ESMO Breast
2026
Live Coverage
Berlin, Germany . May 6 - 8, 2026
256 Tweets . 57 KOLs . 46.6K Impressions
KOL Social Media Perspectives
Top Discussion Leaders
Uğur Özkerim
Uğur Özkerim @UOzkerim
PHERGain-2
109 impressions · 7 likes · 2026-05-06
View on X ↗
[Slide 1]
PHERGain-2 Study Design
TREATMENT
Cohort A
Key eligibility criteria
pCR
Patients ≥ 18 years
ypTO/is
HP (±ET)
Histologically confirmed
x10
ypNO
invasive carcinoma of
Primary Endpoints
the breast
At screening:
Cohort B
No prior treatment for
Central
breast cancer
HER2 IHC 3+*
Breast MRI
ypN0(i+)
HP (±ET)
HER2 status
Surgery
(1) ≥10% HRQoL
ypN0(mol+)
T-DM1 (±ET)
EoS
x8
x10
decline rate
&
ypN1mi
Node-negative status
MRI imaging
(2) 3y-RFI rate
Tumor size 5-30 mm
(MRI)
Cohort C
ECOG PS 0/1
ChT' + T-DM1
LVEF >55%
ypN1-N3
(±ET)
x10
Adequate organ function
HP: 600 mg H plus 1200 mg P loading
dose, then 600 mg H plus 600 mg P
Physician's choice chemotherapy was allowed
maintenance dose q3w
before adjuvant T-DM1
T-DM1: 3.6 mg/kg of body weight q3w
ET up to 5 years and radiotherapy as per
Follow-up"
HR status and institutional practices
PROs
assessments: Baseline
D1C1-C8
≤14d pre-op
Adj D1C1
FU q3m x2y
FU q6m x3y
Annual to EOS

---

[Slide 2]
Conclusion
PHERGain-2 suggests maintenance of HRQoL over one year of treatment, although
interpretation is limited by treatment heterogeneity and lack of a direct comparator
Patients without pCR experienced greater HRQoL deterioration, likely reflecting treatment
escalation (T-DM1 ± chemotherapy)
The pCR rate of 59.6% observed with this chemotherapy-free strategy is encouraging,
particularly in a population including HR-positive disease
The safety profile was consistent with known effects of trastuzumab/pertuzumab and T-DM1
Pending mature efficacy outcomes (3-year RFI), this response-adapted, chemotherapy-free,
strategy appears clinically feasible and may support treatment individualization in selected
low-risk patients
Paolo Tarantino
Paolo Tarantino @PTarantinoMD
PHERGain-2
40 impressions · 0 likes · 2026-05-06
View on X ↗
[Slide 1]
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
PHERGain-2 Study Design
TREATMENT
Key eligibility criteria
Cohort A
pCR
Patients 2 18 years
Histologically confirmed
ypTO/is
HP (±ET)
x10
invasive carcinoma of
ypNO
the breast
Primary Endpoints
No prior treatment for
At screening:
Cohort B
Central
breast cancer
HP (±ET)
HER2 IHC 3+*
x8
Breast MRI
Surgery
ypN0(i+)
HER2 status
T-DM1 (±ET)
(1) >10% HRQoL
ypN0(mol+)
EoS
&
ypN1mi
x10
decline rate
Node-negative status
Tumor size 5-30 mm
MRI imaging
(2) 3y-RFI rate
(MRI)
Cohort C
ECOG PS 0/1
ChT' T-DM1
LVEF >55%
ypN1-N3
(+ET)
Adequate organ function
HP: 600 mg H plus 1200 mg P loading
x10
dose, then 600 mg H plus 600 mg P
Physician's choice chemotherapy was allowed
maintenance dose q3w
before adjuvant T-DM1
T-DM1: 3.6 mg/kg of body weight q3w
ET up to 5 years and radiotherapy as per
Follow-up*
HR status and institutional practices
PROs
assessments: Baseline
D1C1-C8
<14d pre-op
Adj D1C1
FU q3m x2y
FU q6m x3y
Annual to EOS
"According to the 2018 American Society of Clinical Oncology/College of American Pathologists criteria.
TAII patients who were hormonal receptor-positive received ET concomitantly with HP or T-DM1. ET was sex- and menopausal status-based premenopausal and perimenopausal women receive ovanan function suppression plus tamoxifen (20 mg/day
orally) or letrozole (2.5 mg/day orally); postmenopausal women receive letrozole (2.5 mg/day orally): and men receive tamoxifen (20 mg/day orally).
*All patients must be followed up for 5 years from when the last patient has completed surgery (EoS), even if the assigned treatment is discontinued permanently
ChT, chemotherapy, ECOG PS, Eastern Cooperative Oncology Group performance status; d, day, EoS, end of study, ET, endocrine therapy, FU, follow-up; HER2, human epidermal growth factor receptor 2; HP, trastuzumab and pertuzumab; HRQoL. health related quality of
life; IHC, immunohistochemistry, LVEF, left ventricular ejection fraction; m, month; MRI, magnetic resonance imaging pCR pathological complete response; PRO, patient-reported outcomes; RFI, recurrence-free survival; q3w, every three weeks; y. year

---

[Slide 2]
Primary safety endpoint: >10% HRQoL decline rate at one
year
≥10% HRQoL decline rate
Patient-reported outcomes
N = 396 ; n (%)
Completion rate at baseline
391 (98.7)
42.8%
95% CI 36.9-48.8
Baseline HRQoL score, mean (95% CI)
78.6 (76.8-8 0.5)
Completion rate at 1 year
360 (90.9)
HR positive: 45.2% (95% CI 38.3-52.3)
Fisher's exact test
1-year HRQoL score, mean (95% CI)
69.6 (67.5-71.8)
HR negative: 36.1% (95% CI 25.4-47.9)
p 0.11
n (%), number of patients (percentage based on N); N, Number of patients.
Patient reported outcomes were analyzed on patients who received at least one dose of study treatment and completed baseline and at least one follow-up questionnaire 1. year post-neoadjuvant treatment
Patients without a >10% decline at one year who discontinued the study due to disease progression, toxicity or death within the first year after starting neoadjuvant treatment were considered events
Dr. Antonio Llombart-Cussac
Content of this presentation is copyright and responsibility of the author Permission is required for re-use
ESMO
CI, confidence interval; HR, hormone receptor, HRQoL, health-related quality of life

---

[Slide 3]
Secondary endpoint: pCR rate by HR status and tumor size
Median (range) T1 tumor size: 16mm (7-20)
Median (range) T2 tumor size: 23.5mm (21-30)
100
pCR rate
100
100
59.6%
63.0%
59.6%
95% CI 54.6-64.4
95% CI 53.1-72.1
95% CI 53.3-65.7
80
80
80
59.6%
58.3%
Pathological complete response (%)
95% CI 51.0-67.7
95% CI 52.4-64.1
60
60
60
40
40
40
236 / 396
68 / 108
168 / 288
152/255
20
84 141
20
20
0
0
0
All participants
HR-
HR+
T1
T2
Fisher's exact test
Fisher's exact test
p=0.42
P 1.00
Dr. Antonio Liombart-Cussac
Content of this presentation is copyright and responsibility of the author Permission is required for re-use.
ESMO
CI, confidence interval; HR, hormone receptor, pCR pathological complete response

---

[Slide 4]
Conclusion
PHERGain-2 suggests maintenance of HRQoL over one year of treatment, although
interpretation is limited by treatment heterogeneity and lack of a direct comparator
Patients without pCR experienced greater HRQoL deterioration, likely reflecting treatment
escalation (T-DM1 ± chemotherapy)
The pCR rate of 59.6% observed with this chemotherapy-free strategy is encouraging,
particularly in a population including HR-positive disease
The safety profile was consistent with known effects of trastuzumab/pertuzumab. and T-DM1
Pending mature efficacy outcomes (3-year RFI), this response-adapted, chemotherapy-free,
strategy appears clinically feasible and may support treatment individualization in selected
low-risk patients
Dr. Antonio Llombart Cussac
Content of this presentation is copyright and responsibility of the author Permission is required for re-use
ESMD
Abi Siva MD
Abi Siva MD @AbiSivaMD
PHERGain-2
39 impressions · 1 likes · 2026-05-06
View on X ↗
[Slide 1]
2026
ESMO BREAST CANCER
Annual Congress
Chemotherapy-free, pathological
complete response (pCR)-guided strategy
with trastuzumab-pertuzumab. (HP) and
T-DM1 in HER2+ early breast cancer
(EBC): PHERGain-2
Laia Garrigós, Manuel Ruiz-Borrego, José Manuel Pérez-Garcia, Angel Guerrero-Zotano, Alfonso Cortés-
Salgado, Sherko Kümmel, Marco Colleoni, Cristina Reboredo-Rendo, Begoña Bermejo, Isabel Blancas, Joaquin Gavila, Alessandra
Fabi, Olalla Ballesteros, Griselda Martrat, Simona lacobucci, Olga Boix, Pau Berenguer-Molins, Daniel Alcalá-López, Javier
Cortés, Antonio Llombart-Cussac
May 6, 2026

---

[Slide 2]
Content of this presentation is copyright and responsibility of the author Permission is required for re-use.
PHERGain-2 Study Design
TREATMENT
Cohort A
Key eligibility criteria
pCRt
Patients ≥ 18 years
ypTO/is
HP (±ET)
Histologically confirmed
x10
invasive carcinoma of
ypNO
the breast
Primary Endpoints
At screening:
Cohort B
No prior treatment for
Central
HP (±ET)
Breast MRI
ypN0(i+)
breast cancer
HER2 status
Surgery
(1) >10% HRQoL
ypN0(mol+)
T-DM1 (±ET)
EoS
HER2 IHC 3+*
x8
&
ypN1mi
x10
decline rate
Node-negative status
MRI imaging
Tumor size 5-30 mm
(2) 3y-RFI rate
(MRI)
Cohort C
ECOG PS 0/1
ChT + T-DM1
LVEF >55%
ypN1-N3
(±ET)
Adequate organ function
x10
HP: 600 mg H plus 1200 mg P loading
dose, then 600 mg H plus 600 mg P
Physician's choice chemotherapy was allowed
maintenance dose q3w
before adjuvant T-DM1
T-DM1: 3.6 mg/kg of body weight q3w
ET up to 5 years and radiotherapy as per
Follow-up®
HR status and institutional practices
PROs
assessments: Baseline
D1C1-C8
<14d pre-op
Adj D1C1
FU q3m x2y
FU q6m x3y
Annual to EOS
"According to the 2018 American Society of Clinical Oncology/College of American Pathologists criteria.
TAll patients who were hormonal receptor-positive received ET concomitantly with HP or T-DM1. ET was sex- and menopausal status-based: premenopausal and perimenopausal women receive ovarian function suppression plus tamoxifen (20 mg/day
orally) or letrozole (2.5 mg/day orally); postmenopausal women receive letrozole (2.5 mg/day orally); and men receive tamoxifen (20 mg/day orally).
"All patients must be followed up for 5 years from when the last patient has completed surgery (EoS), even if the assigned treatment is discontinued permanently.
ChT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; d, day, EoS, end of study, ET, endocrine therapy, FU, follow-up; HER2, human epidermal growth factor receptor 2; HP, trastuzumab and pertuzumab; HRQoL, health related quality
life; IHC, immunohistochemistry; LVEF, left ventricular ejection fraction; m, month; MRI, magnetic resonance imaging: pCR pathological complete response; PRO, patient-reported outcomes; RFI, recurrence-free survival; q3w, every three weeks; Y. year

---

[Slide 3]
Secondary endpoint: overall pCR rate
100
pCR rate
Patients
Undergoing Surgery
59.6%
N 391
80
95% CI 54.6-64.4
Cohort B
Cohort A
Cohort C
pCR
ypN1-N3
ypN0(mol+), ypN1mi
N = 236
N = 148
Pathological complete response (%)
60
ypN0(i+),
I
N=7
40
236/396
20
Adjuvant Therapy
0
At data cutoff, all patients were receiving the protocol-specified treatment for their assigned cohort
All participants
In Cohort C, two patients received chempotherapy + T-DM1
Dr. Antonio Llombart-Cussac
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
ESMD
CI, confidence interval; pCR, pathological complete response

---

[Slide 4]
Secondary endpoint: pCR rate by HR status and tumor size
Median (range) T1 tumor size: 16mm (7-20)
Median (range) T2 tumor size: 23.5mm (21-30)
100
pCR rate
100
100
59.6%
63.0%
59.6%
95% CI 54.6-64.4
95% CI 53.1-72.1
95% CI 53.3-65.7
80
80
80
59.6%
58.3%
Pathological complete response (%)
95% CI 51.0-67.7
95% CI 52.4-64.1
60
60
60
I
40
40
40
236 / 396
68 / 108
168 / 288
152/255
84 / 141
20
20
20
0
0
0
All participants
HR-
HR+
T1
T2
Fisher's exact test
Fisher's exact test
P 0.42
p=1.00
Dr. Antonio Llombart-Cussac
Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
ESMO
CI, confidence interval; HR, hormone receptor, pCR pathological complete response

PHERGain-2 Top Tweets

Paolo Tarantino @PTarantinoMD
326 imp · 8 likes · 2026-05-06
PHERGain-2: large phase 2 trial in selected patients with small (5-30 mm), HER2 IHC 3+ tumors, shows mostly preserved QoL and a pCR rate of 60% irrespective of HR status with neoadjuvant HP+/-ET x8 cycles. Interesting strategy, pending 3-year RFI results (co-primary endpoint). https://t.co/ORjS4Ys4vj
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Erika Hamilton, MD, FASCO @ErikaHamilton9
260 imp · 6 likes · 2026-05-08
#PHERGain2 took Node neg, <3 cm rumors IHC 3+ tumor's and have HP +/- ET x8 and took to surgery. 59.6% pCR rate. 🎯 up to 60% of pts with node negative disease could maybe avoid cytotoxic therapy?!? #ESMOBreast26 #bcsm @hoperugo https://t.co/h1ZSkfHN6e
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KOL Pulse AI @KolPulseAI
210 imp · 2 likes · 2026-05-07
KOL Updates #ESMOBreast26 Day 2 — Berlin 🔥 TRAIN-4: 73% pCR chemo-free HER2+ neoadj 🔥 PHERGain-2 published in Annals of Onc 🔥 PREcoopERA: giredestrant alone not enough — needs OFS Top KOL voices: @ChandrakanthMv @ErikaHamilton9 @DrSGraff @LoiSher @gaiagriguolo 🚩AI-Native https://t.co/aXJUbVkVP8
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Uğur Özkerim @UOzkerim
109 imp · 7 likes · 2026-05-06
🧬 PHERGain-2 continues to challenge the “chemotherapy for all” paradigm in HER2+ early breast cancer. 🔥A response-adapted, chemotherapy-free strategy achieved: ✅ pCR: 59.6% ✅ Maintained HRQoL over 1 year ✅ Manageable safety profile While long-term efficacy data are still https://t.co/vSrbf9yi8u
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Paolo Tarantino @PTarantinoMD
40 imp · 0 likes · 2026-05-06
PHERGain-2: large phase 2 trial in selected patients with small (5-30 mm), HER2 IHC 3+ tumors, shows mostly preserved QoL and a pCR rate of 60% irrespective of HR status with neoadjuvant HP+/-ET x8 cycles. Interesting strategy, pending 3-year RFI results (co-primary endpoint). https://t.co/sT8hImIkPm
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Abi Siva MD @AbiSivaMD
39 imp · 1 likes · 2026-05-06
PHERGain-2: response-adapted neoadjuvant HP followed by adjuvant T-DM1 for residual disease. This study included patients with small, node negative Her2–3+ tumors. Pleasantly surprised by the high pCR rates, regardless of ER status. Exciting de-escalation signal in HER2+ early https://t.co/27ZczHJtCN
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26 imp · 1 likes · 2026-05-06
Proud to have participated in PHERGain-2 @wearemedsir In T<3cms, N0, HER2 IHC 3+ EBC, CT-free neoadjuvant HP ± ET achieved: ✅ pCR 59.6% ✅ CT-free 99.5% Awaiting 3yiDFS https://t.co/dAQqM0RHKJ
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MUTHUVEERAPPAN S @YesMVchemoMed
22 imp · 0 likes · 2026-05-07
Are we entering the #ChemoFree era in #Her2positive #breastcancer? 👀 PHERGain-2 shows a pCR-guided strategy with trastuzumab–pertuzumab ± endocrine therapy and T-DM1 can achieve impressive pCR rates while preserving HRQoL. 🎯 pCR: 59.6% 🛡️ Low grade ≥3 TRAEs: 5.6% 💡 Smarter https://t.co/e4s72HxpDs
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About the PHERGain-2 Trial

PHERGain-2 is an international, multicentre, open-label Phase II trial evaluating a chemotherapy-free, pCR-guided treatment strategy using trastuzumab-pertuzumab (HP) and T-DM1 in patients with HER2-positive (IHC 3+), node-negative, small (5–30 mm) early breast cancer. Presented at ESMO Breast Cancer 2026 with concurrent publication in Annals of Oncology, the trial enrolled 396 patients across 47 centres in Spain, Italy, Denmark, Hungary, Poland, and Bulgaria. The strategy: all patients received 8 cycles of neoadjuvant trastuzumab + pertuzumab; adjuvant therapy was adapted by pathological response (pCR continued HP; residual disease escalated to T-DM1).

PHERGain-2 Methodology & Results

Population: 396 patients with untreated, centrally confirmed HER2-positive (IHC 3+), node-negative, early breast cancer. Tumours 5–30 mm by central MRI. Median tumour size 18 mm; 72.7% HR+; 61.6% T1; 391 (98.7%) underwent surgery.

Interventions: Neoadjuvant: 8 cycles trastuzumab + pertuzumab (subcutaneous, every 3 weeks). Adjuvant by response: Cohort A (n=236, pCR) — HP to complete 18 cycles; Cohort B (n=148, residual invasive disease or ITC/micromets) — T-DM1 ×10 cycles; Cohort C (n=7, ypN1-3) — optional adjuvant chemo before T-DM1.

Endpoints: Co-primary: 1-year HRQoL decline (≥10% EORTC QLQ-C30 global) and 3-year recurrence-free interval. Secondary: pCR rate, safety, biomarker analyses (ctDNA).

Efficacy — pCR 59.6% chemo-free · QoL preserved · 3-yr RFI pending

pCR was achieved in 236 patients (59.6%) following chemotherapy-free neoadjuvant trastuzumab-pertuzumab. By HR status: 63.0% pCR in HR-negative, 58.3% in HR-positive (no significant difference). By tumour size: 59.6% in both T1 and T2. At 1 year, ≥10% HRQoL decline occurred in 154/360 (42.8%) — significantly lower among pCR patients (37.3%) than non-pCR T-DM1 cohort (51.9%). The 3-year recurrence-free interval primary endpoint remains immature.

Safety & Tolerability — Mild-moderate TRAEs; 0.3% T-DM1 pneumonitis death

Treatment-related adverse events of any grade reported in 86.6% of patients; grade ≥3 in 5.6%; serious AEs in 6.1%. One patient (0.3%) died from T-DM1-related pneumonitis, underscoring that de-escalation strategies still require careful monitoring when ADCs are deployed. Only 2 patients (0.5%) discontinued for disease progression.

Clinical Implications

Rishabh Jain summarized PHERGain-2 as testing “a pCR-guided strategy with HP ± T-DM1,” with key findings “pCR: 59.6%,” “Similar across HR+ / HR-,” and “HRQoL maintained,” while flagging that “3-year RFI still immature.” Aya Mohamed framed the result as “Chemotherapy Free Dual HER2 Blockade Achieves ~60% pCR with Preserved HRQoL—Operationalizing a De-escalation, ‘Minimum Effective Treatment’ Strategy in Low Risk HER2+ Early #BreastCancer.” The OCR-confirmed conclusions slide from presenter Antonio Llombart-Cussac characterizes the chemotherapy-free strategy as encouraging in a population that includes HR-positive disease, with mature efficacy outcomes (3-year RFI) still pending. The central caveat remains: this response-adapted approach may support treatment individualization in selected low-risk patients only once the recurrence endpoint matures.

PHERGain-2 in the News

Key KOL Sentiments — PHERGain-2

HandleNameSentimentTweet (excerpt)Imp.
@PTarantinoMD Paolo Tarantino Neutral PHERGain-2: large phase 2 trial in selected patients with small (5-30 mm), HER2 IHC 3+ tumors, shows mostly preserved Qo… 326
@ErikaHamilton9 Erika Hamilton, MD, FASCO Neutral #PHERGain2 took Node neg, <3 cm rumors IHC 3+ tumor's and have HP +/- ET x8 and took to surgery. 59.6% pCR rate. 🎯 up… 260
@KolPulseAI KOL Pulse AI Neutral KOL Updates #ESMOBreast26 Day 2 — Berlin 🔥 TRAIN-4: 73% pCR chemo-free HER2+ neoadj 🔥 PHERGain-2 published in Annals of … 210
@UOzkerim Uğur Özkerim Neutral 🧬 PHERGain-2 continues to challenge the “chemotherapy for all” paradigm in HER2+ early breast cancer. 🔥A response-adapt… 109