PATINA (AFT-38; NCT02947685) is an open-label phase 3 trial that added palbociclib (IBRANCE; Pfizer) to maintenance trastuzumab (± pertuzumab) plus endocrine therapy after induction in HR+/HER2+ metastatic breast cancer: investigator-assessed PFS HR 0.76 (95% CI 0.59–0.97), with Grade ≥3 neutropenia in 61% (FDA label). FDA approved June 24, 2026; Japan approved September 16, 2026; EU application withdrawn September 15, 2026.
Posts by physicians about PATINA during ESMO 2026 week (October 17–24, 2026). Each post is shown in full and verbatim, sorted by reach and linked to the original on X.
FDA APPROVED June 24, 2026 — maintenance treatment following induction, HR+/HER2+ locally advanced or metastatic breast cancer
The FDA approved palbociclib (Ibrance, Pfizer Inc.) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adults with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment.
Design: palbociclib + trastuzumab (± pertuzumab) + endocrine therapy as maintenance after first-line induction, vs anti-HER2 + endocrine therapy alone (HR+/HER2+ MBC).
PFS: Investigator-assessed median PFS 44.3 vs 29.1 months; HR 0.75 (95% CI 0.59–0.96; two-sided P=0.02) (NEJM 2026). FDA label: HR 0.76 (95% CI 0.59–0.97; one-sided p=0.0134); median PFS "cannot be adequately described because of censoring."
Safety: Grade ≥3 neutropenia 61%; serious adverse reactions 25%; fatal adverse reactions 1.2%; palbociclib permanently discontinued for adverse reactions in 18% (FDA label, palbociclib arm n=260).
Regulatory: FDA approved June 24, 2026; Japan approved September 16, 2026. EU: Pfizer withdrew its application on September 15, 2026; at that time the EMA’s provisional opinion was that the change "could not have been authorised" (EMA Q&A, October 16, 2026). Not approved in the EU for HR+/HER2+ disease; the EMA states there are no consequences for Ibrance in its authorised uses (HR+/HER2−).
Design caveat: Open-label trial; the primary endpoint was investigator-assessed PFS. The EMA stated that differences between investigator assessments and an independent review of the scans "raised concerns that the results may have been biased in favour of Ibrance" and that the independent review "did not confirm a clear improvement" (EMA Q&A, October 16, 2026).
Trial: Alliance Foundation Trials (AFT-38), funded by Pfizer; PI Otto Metzger; NCT02947685.
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 24, 2026.
Regulatory Update: EMA
PATINA in the EU: Application Withdrawn
EU: APPLICATION WITHDRAWN EU application withdrawn (September 15, 2026). EMA: at the time of withdrawal, the benefits "had not been demonstrated"
Pfizer Europe MA EEIG withdrew its type II variation application (EMA/VR/0000316536) to extend the use of Ibrance to "the maintenance treatment of adults with HR-positive, HER2-positive locally advanced or metastatic breast cancer" on September 15, 2026. The CHMP's draft agenda for its September 14–17, 2026 meeting listed an oral explanation on this procedure for September 15, 2026. (EMA Q&A, October 16, 2026; Pfizer withdrawal letter, September 15, 2026; CHMP draft agenda, September 14–17, 2026)
"At the time of the withdrawal, based on its review of the information and the company’s response to its questions, the Agency had concerns and its provisional opinion was that the change to Ibrance’s marketing authorisation could not have been authorised. The Agency considered that the study did not provide sufficiently reliable evidence that Ibrance was effective in the proposed use. The study was open-label, meaning that the patients and the doctors carrying out the study knew which treatment was being given. The main assessment of whether the cancer had worsened was made by these doctors, and differences between their assessments and an independent review of the scans raised concerns that the results may have been biased in favour of Ibrance. The independent review did not confirm a clear improvement, and the other measures of effectiveness did not provide sufficient supporting evidence. Therefore, at the time of the withdrawal, the Agency’s opinion was that the benefits of Ibrance in the maintenance treatment of HR-positive, HER2-positive locally advanced or metastatic breast cancer had not been demonstrated." (EMA Q&A, EMA/VR/0000316536, October 16, 2026)
"This withdrawal is to allow for additional data collection and analyses to address the questions raised by the Committee for Medicinal Products for Human Use (CHMP). This withdrawal does not have any impact on ongoing clinical trials with palbociclib. Pfizer Europe MA EEIG reserves the right to make a further submission at a future date in this or other therapeutic indication(s)." (Pfizer Europe MA EEIG letter to EMA, September 15, 2026)
Per the EMA, "There are no consequences for Ibrance in its authorised uses" (HR-positive, HER2-negative breast cancer), and the company informed the Agency that there are no consequences for patients in clinical trials receiving Ibrance. The withdrawal concerns the EU application only; the FDA (June 24, 2026) and Japanese (September 16, 2026) approvals were separate regulatory decisions.
On September 16, 2026, Japan approved palbociclib as maintenance therapy after chemotherapy for HR-positive, HER2-positive unresectable or recurrent breast cancer (English translation), in combination with trastuzumab (with or without pertuzumab) and endocrine therapy, based on PATINA (Pfizer Japan press release, September 16, 2026).
Indication as published by Pfizer Japan (in Japanese): 「ホルモン受容体陽性かつHER2陽性の手術不能又は再発乳癌における化学療法後の維持療法」
Where PATINA Fits: Sequencing, Guidelines and Practice
Posts from breast oncologists since September 2026 on where palbociclib maintenance fits alongside DESTINY-Breast09 and HER2CLIMB-05, how guidelines treat it, and what it looks like in clinic. Quoted verbatim; Japanese posts are shown as written.
[Slide 1]
SAN ANTONIO
BREAST CANCER
AFT-38 PATINA Study Design
SYMPOSIUM
UT Health
AACR
Men Cancer Center
-
Registration
Key eligibility criteria
Palbociclib (125 mg PO QD
Histologically confirmed
D1-D21)
HR+,HER2+ mBC
Completion of induction
N=518
Trastuzumab I pertuzumab +
No prior treatment in the
chemotherapy and no
endocrine therapy*
advanced setting beyond
evidence of disease
R
Until PD
or
induction treatment
progression (i.e., CR, PR,
1:1
toxicity
.
6-8 cycles of treatment,
or SD)
including trastuzumab +
Trastuzumab + pertuzumab +
endocrine therapy*
pertuzumab and
taxane/vinorelbine
Stratification factors
Pertuzumab use (yes vs no)
The non-pertuzumab option is limited to up to 20% of the population
Prior anti-HER2 therapy in the (neo)adjuvant setting (yes vs no, including de novo)
Response to induction therapy (CR or PR vs SD) by investigator assessment
Type of endocrine therapy (fulvestrant vs aromatase inhibitor)
*Trastuzumab and pertuzumab were administered per SOC. Endocrine therapy options include an aromatase inhibitor or fulvestrant. Factors used in stratified analyses.
CR=complete response; D=day; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; mBC=metastatic breast cancer; PD=progressive disease; PO=orally;
PR=partial response; QD=once a day; R=randomization; SD=stable disease; SOC=standard of care.
---
[Slide 2]
SAN ANTONIO
BREAST CANCER
Conclusions
SYMPOSIUM
UT Health
AACR
lan Antonio
American Association
Care -
Mays Cancer Center
Our results reinforce the strong scientific rationale for overcoming
resistance to anti-HER2 therapy and endocrine therapy by adding CDK4/6
inhibition
The addition of palbociclib to anti-HER2 and endocrine therapy
demonstrated a statistically significant improvement in PFS in patients
diagnosed with HR+,HER2+ advanced breast cancer in the first-line
metastatic setting
Palbociclib added to anti-HER2 and endocrine therapy had a manageable
toxicity profile and without new safety signals
CDK4/6=cyclin-dependent kinase 4/6; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; PFS=progression-free survival.
[Slide 1]
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
SAN ANTONIO
BREAST CANCER
Implications to Clinical Practice
SYMPOSIUM
UT Health
AACR
-
-
Ment -
The AFT-38 PATINA phase III study demonstrates a clinically meaningful
improvement in PFS among patients diagnosed with HR+, HER2+
breast cancer
Median PFS increased from 29.1 to 44.3 months (A15.2 months)
Manageable toxicity
Palbociclib added to anti-HER2 and endocrine therapy may
represent a new standard of care for patients diagnosed with
HR+, HER2+ advanced breast cancer
HER2=human epidermal growth factor receptor 2; HR=hormone receptor; PFS=progression-free survival.
This presentation is the intellectual property or the author/presenter. Contact them at Dto for permission to reprint and/or distribute
[Slide 1]
BRINGING THE WORLD OF EP TOGETHER
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
Secondary endpoint: Overall Survival
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
(interim analysis)
UT Health
AACR
-
- -
100
90
80
70
60
Final overall survival
50
analysis requires 247
Palbociclib Anti-
Anti-HER2 and
40
HER2 and ET
ET
events. Only 119
Events
58/261
61/257
30
Median in mos (95% CI)
NE (71.6 NE)
77 (72-NE)
observed thus far.
3-yr os, %. 95% CI
87 (82.8-91.2)
84.7 (80-89.3)
20
5-yr OS, %. 95% CI
74.3 (67.7-80.9)
69.8 (62.4-77.2)
10
Hazard ratio (95% CI)
0.86 (0.6-1.24)
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
Time (months)
"Kaplan-
Patients at-Risk
Meier method: Unstratified
Palbo HER2 ET
261
255
248
239
229
220
207
187
146
101
60
22
7
I
0
Cox model; Cl=confidence
HER2 ET
257
235
228
221
215
197
188
167
125
90
49
22
6
0
interval: NE=not evaluable;
OS=overall survival;
DECEMBER 10-14,2024 * SAN ANTONIO
---
[Slide 2]
BRINGING THE WORLD OF EP TOGETHER
2
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
SAN ANTONIO
BREAST CANCER
AFT-38 PATINA
SYMPOSIUM
UT Health
AACR
Key eligibility criteria
Palbociclib (125 mg PO QD D1-
Pre-Study
D21)
Histologically confirmed
Completion of induction
N=518
Trastuzumab + Pertuzumab +
HR+HER2+ MBC
chemotherapy and no
Endocrine therapy
R*
Until PD
No prior treatment in the
evidence of disease
or
advanced setting beyond
progression (i.e. , CR, PR,
1:1
toxicity
induction treatment
or SD)
Trastuzumab * Pertuzumab +
6-8 cycles of treatment,
Endocrine therapy
including trastuzumab I
pertuzumab and taxane
Start of Study AFTER Induction
Patients who experienced disease progression
during induction or screening were not
included in study. Patients with de novo
resistance were eliminated
Metzger o et al. SABCS 2024
DECEMBER 10 14, 2024 * SAN ANTONIO
[Slide 1]
&
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
SAN ANTONIO
BREAST CANCER
Implications to Clinical Practice
SYMPOSIUM
UT Health
AACR
-
MayCamerCom
The AFT-38 PATINA phase III study demonstrates a clinically meaningful
improvement in PFS among patients diagnosed with HR+,HER2+
breast cancer
Median PFS increased from 29.1 to 44.3 months (A15.2 months)
Manageable toxicity
Palbociclib added to anti-HER2 and endocrine therapy may
represent a new standard of care for patients diagnosed with
HR+,HER2+ advanced breast cancer
HER2=human epidermal growth factor receptor 2: HR=hormone receptor PFS=progression-free survival.
This presentation is the intelectual property of the author/presenter Contact them at Other CL for permission to reprint and/or distribute
---
[Slide 2]
SAN ANTONIO
BREAST CANCER
Conclusions
SYMPOSIUM
UT Health
AACR
Sex Annoid
American Association
Mays Cancer Center
for Cancer Research
Our results reinforce the strong scientific rationale for overcoming
resistance to anti-HER2 therapy and endocrine therapy by adding CDK4/6
inhibition
The addition of palbociclib to anti-HER2 and endocrine therapy
demonstrated a statistically significant improvement in PFS in patients
diagnosed with HR+,HER2+ advanced breast cancer in the first-line
metastatic setting
Palbociclib added to anti-HER2 and endocrine therapy had a manageable
toxicity profile and without new safety signals
CDK4/6=cyclin-dependent kinase 4/6; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; PFS=progression-free survival.
---
[Slide 3]
Primary Endpoint: PFS
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
(Investigator-Assessed)
UT Health
AACR
San Americ
Mays Cancer Center
for Cancer Research
100
93.6%
Palbo + anti-HER2
Anti-HER2
and ET
90
and ET
84.9%
87.9%
Events
126/261
136/257
80
Median PFS, months (95% CI)
44.3 (32.4-60.9)
29.1 (23.3-38.6)
73.4%
70
Hazard ratio (95% CI)
0.74 (0.58-0.94)
65.4%
Nominal 1-sided P value
0.0074
60
55.2%
50
46.9%
43.2%
40
38.2%
HH
30
33.4%
20
10
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
Time (months)
Cl=confidence interval; ET=endocrine therapy;
Patients-at-Risk
HER2=human epidermal growth factor receptor 2;
Palbo + HER2
261
231
203
168
146
128
113
94
78
55
33
14
4
1
0
palbo=palbociclib.
HER2 ET
257
198
159
137
116
102
87
68
51
29
14
6
1
0
---
[Slide 4]
SAN ANTONIO
BREAST CANCER
AFT-38 PATINA Study Design
SYMPOSIUM
UT Health
AACR
Sen Antonio
American Association
for Cancer Research
Mays Cancer Center
Registration
Key eligibility criteria
Palbociclib (125 mg PO QD
Histologically confirmed
D1-D21)
HER2+ mBC
Completion of induction
N=518
Trastuzumab + pertuzumab +
No prior treatment in the
chemotherapy and no
endocrine therapy*
advanced setting beyond
R
Until PD
evidence of disease
or
induction treatment
progression (i.e., CR, PR,
1:1
toxicity
SURVIVAL
FOLLOW-UP
6-8 cycles of treatment,
or SD)
including trastuzumab +
Trastuzumab + pertuzumab +
pertuzumab and
endocrine therapy*
taxane/vinorelbine
Stratification factors
Pertuzumab use (yes VS no)
The non-pertuzumab option is limited to up to 20% of the population
Prior anti-HER2 therapy in the (neo)adjuvant setting (yes VS no, including de novo)+
Response to induction therapy (CR or PR VS SD) by investigator assessment
Type of endocrine therapy (fulvestrant VS aromatase inhibitor)
*Trastuzumab and pertuzumab were administered per SOC. Endocrine therapy options include an aromatase inhibitor or fulvestrant. Factors used in stratified analyses.
CR=complete response; D=day; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; mBC=metastatic breast cancer; PD=progressive disease; PO=orally;
PR=partial response; QD=once a day; R=randomization; SD=stable disease; SOC=standard of care.
[Slide 1]
QUESTIONS AHEAD OF
DESTINY-Breast09 AT ASCO 2025
1. How strong will the benefit be?
1. PATINA vs. CLEOATRA
2. Is sequential T-Dxd use an option?
1. os differential between 1st line - 2nd line
3. What to give after T-Dxd?
4. Proionged T-Dxd use and managing
ILD risk
[Slide 1]
SAN ANTONIO
Primary Endpoint: PFS
BREAST CANCER
SYMPOSIUM
UT Health AACR
(Investigator-Assessed)
butes
-
I I I
100
Palbo + anti-HER2
Anti-HER2
93.6%
and ET
and ET
90
84.9%
Events
126/261
136/257
87.9%
so
Median PFS, months (95% CI)
44.3 (32.4-60.9)
29.1 (23.3-38.6)
73.4%
Hazard ratio (95% CI)
0.74 (0.58-0.94)
70
Percent alive and disease-free
65.4%
Nominal 1-sided P value
0.0074
60
55.2%
46.9%
50
43.2%
40
38.2%
33.4%
30
20
10
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
Time (months)
Cl=confidence Interval; ET=endocrine therapy;
Patients-at-Risk
HER2=human epidermal growth factor receptor 2;
Pabo . HER2 ET
261
231
203
168
146
128
113
94
78
55
33
14
4
I
0
palbo=palbociclib.
HER2 ET
257
198
159
137
116
102
87
68
51
29
14
6
I
0
This presentation is the intellectual property of the authoripresenter Contact them at Offe for permission to reprint and/or distribute
i
,
,
PATINA (AFT-38; NCT02947685) is a randomized, open-label phase 3 trial of palbociclib added to maintenance anti-HER2 therapy and endocrine therapy after induction in HR+/HER2+ metastatic breast cancer. Global sponsor: Alliance Foundation Trials, LLC; Pfizer provided funding; conducted with six international cancer research groups (PrECOG, Unicancer, GBG, Fondazione Michelangelo, SOLTI, Breast Cancer Trials). (Pfizer press release, June 24, 2026; ClinicalTrials.gov NCT02947685)
KOL discussion spans multiple conferences with 89 tracked physician posts from 40 oncology opinion leaders generating 338.8K total impressions (as of October 22, 2026).
Phase 3, randomized (1:1), open-label, international trial evaluating palbociclib added to maintenance anti-HER2 and endocrine therapy after induction chemotherapy in HR+/HER2+ metastatic breast cancer. Sponsored by Alliance Foundation Trials.
Population
Adults with HR-positive, HER2-positive metastatic breast cancer who completed 4-8 cycles of induction chemotherapy plus HER2-targeted therapy without disease progression.
Interventions
Ibrance (palbociclib) plus anti-HER2 therapy (trastuzumab with or without pertuzumab) plus endocrine therapy versus anti-HER2 therapy plus endocrine therapy alone.
SABCS 2024 (GS2-12, first presentation; Metzger): median 44.3 vs 29.1 months; HR 0.74 (95% CI 0.58–0.94); nominal one-sided P=0.0074 (described as "unstratified 1-sided" in Pfizer’s December 12, 2024 release); 126/261 vs 136/257 events (SABCS 2024 slide).
NEJM 2026;394:451–462 (median follow-up 53.5 months): median 44.3 vs 29.1 months; HR 0.75 (95% CI 0.59–0.96); two-sided P=0.02.
FDA label (June 2026): HR 0.76 (95% CI 0.59–0.97); one-sided p=0.0134; 124/261 (47.5%) vs 133/257 (51.8%) events; "Median PFS cannot be adequately described because of censoring."
Overall survival (secondary endpoint) is immature. SABCS 2024 interim analysis (119 of the 247 events required for the final OS analysis; SABCS 2024 slide, Metzger): 58/261 vs 61/257 events; median not estimable (95% CI 71.6–NE) vs 77 months (95% CI 72–NE); 5-year OS 74.3% vs 69.8%; HR 0.86 (95% CI 0.6–1.24; unstratified Cox model per slide footnote). FDA label: "At the time of the PFS analysis, OS data were not mature with 24% deaths in the overall population."
FDA label (safety population 509; palbociclib arm n=260): neutropenia 78% (Grade ≥3 61%); febrile neutropenia 0.8%; ILD/pneumonitis 1% (no Grade 3, 4 or fatal cases); diarrhea 70% (Grade 3 10%) vs 37% (Grade 3 1.2%) with control; serious adverse reactions 25%; fatal adverse reactions 1.2% (including death, hepatic hemorrhage and sepsis, 0.4% each). Adverse reactions led to palbociclib dose interruption in 70%, dose reduction in 53% and permanent discontinuation in 18%. NEJM 2026: grade 3 and grade 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the palbociclib group (vs 30.6% and 3.6%).
Regulatory status differs by region: approved in the US (June 24, 2026) and Japan (September 16, 2026); in the EU, Pfizer withdrew its application, and the EMA stated that at the time of withdrawal the benefits had not been demonstrated (EMA Q&A, October 16, 2026). The benefit comes with more toxicity: Grade ≥3 neutropenia in 61% and permanent palbociclib discontinuation for adverse reactions in 18% (FDA label). The open-label design and investigator-assessed primary endpoint are central to the debate; see the physician reaction in the EMA Update section. [FDA notice][EMA Q&A]
FAQ
PATINA: Frequently Asked Questions
What is the PATINA trial?
PATINA (AFT-38) is a randomized Phase 3 trial testing whether adding palbociclib (IBRANCE) to maintenance anti-HER2 therapy (trastuzumab, with or without pertuzumab) plus endocrine therapy improves outcomes versus anti-HER2 therapy plus endocrine therapy alone, after first-line induction chemotherapy, in HR-positive, HER2-positive metastatic breast cancer.
What were the PATINA progression-free survival results?
Investigator-assessed median PFS was 44.3 versus 29.1 months (HR 0.75; 95% CI 0.59–0.96; two-sided P=0.02; NEJM 2026). The SABCS 2024 presentation reported HR 0.74 (nominal one-sided P=0.0074). The FDA label reports HR 0.76 (95% CI 0.59–0.97; one-sided p=0.0134) and states that median PFS "cannot be adequately described because of censoring." Toxicity was higher with palbociclib: Grade ≥3 neutropenia occurred in 61% (FDA label).
Is palbociclib FDA approved for HER2-positive breast cancer?
Yes, in one HER2-positive setting: on June 24, 2026, the FDA approved palbociclib (IBRANCE) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adults with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment, based on PATINA (investigator-assessed PFS HR 0.76; 95% CI 0.59–0.97; one-sided p=0.0134).
Is palbociclib approved in Europe for HR+/HER2+ breast cancer?
No. Pfizer Europe MA EEIG withdrew its EU application on September 15, 2026, stating the withdrawal was "to allow for additional data collection and analyses to address the questions raised by the Committee for Medicinal Products for Human Use (CHMP)." In its October 16, 2026 Q&A, the EMA said its provisional opinion at the time of withdrawal was that the change "could not have been authorised": the study was open-label, differences between investigator assessments and an independent review of the scans "raised concerns that the results may have been biased in favour of Ibrance," and the independent review "did not confirm a clear improvement." The EMA states there are no consequences for Ibrance in its authorised uses (HR-positive, HER2-negative breast cancer).
Is palbociclib approved in Japan for HR+/HER2+ breast cancer?
Yes. On September 16, 2026, Japan approved palbociclib as maintenance therapy after chemotherapy for HR-positive, HER2-positive unresectable or recurrent breast cancer (English translation), in combination with trastuzumab (with or without pertuzumab) and endocrine therapy, based on PATINA (Pfizer Japan press release, September 16, 2026).
What is the FDA-approved PATINA regimen and dose?
Palbociclib (IBRANCE) plus trastuzumab (Herceptin), with or without pertuzumab (Perjeta), plus endocrine therapy, as maintenance following induction. The palbociclib dose is 125 mg orally once daily for 21 days, followed by 7 days off, in 28-day cycles.
Who sponsored PATINA and what is its trial identifier?
PATINA (AFT-38) was sponsored by Alliance Foundation Trials and funded by Pfizer; the principal investigator was Otto Metzger. Its ClinicalTrials.gov identifier is NCT02947685.
