Pertuzumab

First and only CDK4/6 inhibitor approved for HR+ metastatic disease regardless of HER2 status Approval based on data from the collaborative Phase 3 PATINA trial, which showed a 24% risk reduction in disease progression for IBRANCE added to anti-HER2 and endocrine therapies Continues decade-long legacy of IBRANCE helping transform the treatment for HR+ metastatic breast cancer NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced the U.S. Food and Drug Administration (FDA) approved IBRANCE® (palbociclib) in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) locally advanced or metastatic breast cancer (MBC) following induction treatment. The approval is based on positive results from the Alliance Foundation Trials, LLC (AFT)-sponsored Phase 3 PATINA trial. “Over the past decade, IBRANCE has helped transform metastatic breast cancer treatment, establishing CDK4/6 inhibition as a cornerstone of care,” said Aamir Malik, Chief U.S. Commercial Officer and Executive Vice President, Pfizer. “With today’s FDA approval, IBRANCE becomes the first and only CDK4/6 inhibitor indicated for patients with HR+ metastatic breast cancer regardless of HER2 status, extending its impact to patients who continue to face challenges with treatment resistance. This milestone strengthens confidence in IBRANCE as a CDK4/6 inhibitor backbone across combination regimens, reflecting Pfizer's ongoing leadership in delivering meaningful advances for people with breast cancer.” The PATINA trial demonstrated a 24% reduction in the risk of progression or death following induction treatment with the addition of IBRANCE to anti-HER2 (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapies compared to anti-HER2 and endocrine therapies alone (HR: 0.76 [95% CI, 0.59, 0.97]; one-sided p=0.0134). The safety and tolerability of IBRANCE in PATINA were consistent with its known safety profile. The most commonly reported adverse events with IBRANCE were hematologic toxicities, such as white blood cell decreased and neutrophil count decreased. Non-hematologic adverse events included diarrhea, infections, stomatitis, and fatigue, which were generally mild to moderate in severity. Results from the trial were previously published by AFT in the New England Journal of Medicine and presented at the 2024 San Antonio Breast Cancer Symposium. “Resistance to dual anti-HER2 and endocrine therapy remains a central clinical challenge for patients with HR+, HER2+ metastatic breast cancer – even after an excellent response to initial treatment,” said Otto Metzger, M.D., principal investigator of the trial for Alliance Foundation Trials and Medical Oncologist at the Dana-Farber Cancer Institute. “Based on the results from the PATINA study, the addition of IBRANCE in the maintenance phase can meaningfully extend the time patients go without their disease progressing. This approval gives oncologists a new, evidence-based option to optimize maintenance therapy for their patients with HR+, HER2+ disease.” Approximately 10% of all breast cancers are HR+, HER2+,i which is sometimes referred to as double-positive or triple-positive breast cancer. Historically, there has been limited research specifically focused on the HR+, HER2+ subtype in MBC, and PATINA is the first registrational study to explore the potential of CDK4/6 inhibition in this subtype. Since its initial regulatory approval in 2015, IBRANCE continues to be a standard-of-care first-line treatment for HR+, HER2- MBC and has been prescribed to more than 900,000 patients and approved in more than 100 countries. About the PATINA Trial PATINA (AFT-38) was a randomized, open-label global Phase 3 study to evaluate the efficacy and safety of IBRANCE® (palbociclib) in combination with anti-HER2 therapy (trastuzumab or trastuzumab plus pertuzumab) and endocrine therapy compared to anti-HER2 therapy and endocrine therapy alone as a first-line maintenance therapy (following induction treatment) for patients with HR+, HER2+ MBC. While Pfizer provided funding support for the trial, PATINA was also supported by an academic collaboration led by Alliance Foundation Trials, LLC (AFT) as the global sponsor in partnership with six international cancer research groups in the U.S.(PrECOG), France (French Breast Cancer Intergroup Unicancer), Germany (GBG), Italy (Fondazione Michelangelo), Portugal and Spain (SOLTI), and Australia and New Zealand (Breast Cancer Trials). Study participants who received a median of 6 cycles of induction treatment were randomized to receive IBRANCE, in addition to anti-HER2 therapy and endocrine therapy (n=261), or anti-HER2 therapy and endocrine therapy alone (n=257). The primary endpoint was progression-free survival (PFS) as assessed by the investigator. Overall survival is a secondary endpoint and is not yet mature. About IBRANCE® (palbociclib) IBRANCE is an oral inhibitor of CDKs 4 and 6,ii which are key regulators of the cell cycle that trigger cellular progression.iii,iv In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy; or with fulvestrant in patients with disease progression following endocrine therapy. IBRANCE is indicated in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. IBRANCE is also indicated in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with HR-positive, HER2-positive locally advanced or metastatic breast cancer following induction treatment. IMPORTANT SAFETY INFORMATION Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. In PATINA, neutropenia was the most frequently reported adverse reaction with an incidence of 78%, and Grade ≥3 neutropenia was reported in 61% of patients receiving IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy. Based on laboratory findings, 93% had a decrease in neutrophil counts including 47% with Grade 3 and 3.1% with Grade 4. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Febrile neutropenia has been reported in 0.8% of patients exposed to IBRANCE in the PATINA study. Inform patients to promptly report any fever. Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. In PATINA, 1% of IBRANCE-treated patients had ILD/pneumonitis of any grade and no Grade 3, 4, or fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis. Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants. The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%). The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%). Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), increased blood creatinine (96% vs 91%), decreased neutrophils (95% vs 20%), decreased hemoglobin (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%). The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%). The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%). Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), increased blood creatinine (95% vs 82%), decreased hemoglobin (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%). Serious adverse reactions occurred in 24% of patients in INAVO120 who received IBRANCE plus inavolisib and fulvestrant. Serious adverse reactions occurring in ≥1% of patients receiving IBRANCE plus inavolisib and fulvestrant included anemia (1.9%), diarrhea (1.2%), and urinary tract infection (1.2%). Fatal adverse reactions occurred in 3.7% of patients in INAVO120 who received IBRANCE plus inavolisib and fulvestrant, including (0.6% each) acute coronary syndrome, cerebral hemorrhage, cerebrovascular accident, COVID-19 infection, and gastrointestinal hemorrhage. The most (≥20%)common adverse reactions occurring in INAVO120, including laboratory abnormalities, for IBRANCE plus inavolisib and fulvestrant vs IBRANCE plus placebo and fulvestrantwere decreased neutrophils (95% vs 97%), decreased hemoglobin (88% vs 85%), increased fasting glucose (85% vs 43%), decreased platelets (84% vs 71%), decreased lymphocytes (72% vs 68%), stomatitis (51% vs 27%), diarrhea (48% vs 16%), decreased calcium (42% vs 32%), fatigue (38% vs 25%), decreased potassium (38% vs 21%), increased creatinine (38% vs 30%), increased alanine aminotransferase (34% vs 29%), alkaline phosphatase increased (31% vs 23%), nausea (28% vs 17%), decreased sodium (28% vs 19%), decreased magnesium (27% vs 21%), rash (26% vs 19%), decreased appetite (24% vs 9%), COVID-19 infection (23% vs 10%), and headache (22% vs 14%). Serious adverse reactions occurred in 25% of patients in PATINA who received IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy. Serious adverse reactions in ≥1% of patients receiving IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy included infections (8%), headache and pyrexia (1.5% each), and femur fracture (1.2%). Fatal adverse reactions occurred in 1.2% of patients in PATINA who received IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy including (0.4% each) death, hepatic hemorrhage, and sepsis. The most common adverse reactions (≥20%) occurring in PATINA, including laboratory abnormalities, for IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy vs trastuzumab, with or without pertuzumab, and endocrine therapy were white blood cell decreased (94% vs 25%), neutrophil count decreased (93% vs 19%), creatinine increased (92% vs 87%), hemoglobin decreased (81% vs 47%), diarrhea (70% vs 37%), infections (64% vs 43%), platelet count decreased (59% vs 6%), stomatitis (44% vs 11%), aspartate aminotransferase increased (39% vs 25%), decreased calcium (39% vs 30%), alanine aminotransferase increased (38% vs 28%), decreased potassium (33% vs 17%), fatigue (32% vs 21%), alkaline phosphatase increased (31% vs 23%), nausea (30% vs 15%), asthenia (27% vs 21%), headache (26% vs 18%), rash (22% vs 17%), pruritus (21% vs 17%), and muscle spasms (20% vs 11%). Other Clinical Trials Experience: venous thromboembolism has been reported as an adverse reaction following administration of IBRANCE. Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure. For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis. The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here. There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancers, genitourinary cancers, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . Disclosure Notice The information contained in this release is as of June 24, 2026. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer Oncology, IBRANCE® (palbociclib) and an approval in the U.S. for a new indication for IBRANCE in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with HR+, HER2+ locally advanced or metastatic breast cancer following induction treatment, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of IBRANCE; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the PATINA trial will meet the secondary endpoint for overall survival; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in particular jurisdictions for IBRANCE for HR+, HER2+ metastatic breast cancer or any other potential indications; whether and when any such applications may be approved by regulatory authorities, which will depend on a myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether IBRANCE will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of IBRANCE; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2025, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. References i Kay C, Martinez-Peréz C, Meehan J, et al. Current trends in the treatment of HR+/HER2+ breast cancer. Future Oncol. 2021;17(13):1665-1681. ii IBRANCE (palbociclib) Prescribing Information. New York. NY: Pfizer Inc: April 2025. iii Weinberg, RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329. iv Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22. Media Contact: PfizerMediaRelations@Pfizer.com (link sends email) Investor Contact: IR@Pfizer.com(link sends email) Source: Pfizer Inc.

Filing acceptance, under priority review, based on phase III data showing giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with standard-of-care endocrine therapy 1 Giredestrant represents the first significant advance in adjuvant endocrine therapy in over 20 years 1-3 Giredestrant has the potential to become a new standard-of-care in the adjuvant setting; more than 90% of ER-positive breast cancer cases are diagnosed at an early-stage (I-III) 4-7 The FDA has set a Prescription Drug User Fee Act date of 30 November 2026 Basel, 02 June 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) announced today that the United States (US) Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) under Priority Review for giredestrant, an investigational oral selective oestrogen receptor degrader (SERD), as an adjuvant treatment for adults with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, stage I, II, and III breast cancer. The FDA is expected to make a decision on the approval by 30 November 2026. “Giredestrant represents the first major endocrine therapy advance in early-stage ER-positive breast cancer in decades, where the chance for cure is highest,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “The FDA’s filing acceptance brings us closer to delivering a new standard-of-care with the potential to fundamentally change the treatment paradigm for people with early-stage disease.” The filing acceptance is based on the phase III lidERA Breast Cancer study results, which showed adjuvant giredestrant significantly reduced the risk of invasive disease recurrence or death (iDFS) by 30% compared with standard-of-care endocrine therapy (SoC ET) (hazard ratio [HR]=0.70, 95% confidence interval [CI] 0.57-0.87, p=0.0014). 1 At three years, 92.4% of patients in the giredestrant arm were alive and free of invasive disease versus 89.6% in the SoC ET arm. 1 The iDFS benefit was consistent across all clinically relevant subgroups. 1 Overall survival (OS) data were immature at the time of this analysis, but a clear positive trend was observed. 1 Follow-up for OS will continue to the next analysis. Giredestrant was well tolerated; adverse events were manageable and consistent with its known safety profile. 1 The treatment discontinuation rate for giredestrant was 5.3% versus 8.2% with SoC ET. 1 Additional analyses from the giredestrant programme were presented at the 2026 American Society of Clinical Oncology Congress. This growing body of evidence continues to reinforce the clinical benefit pro giredestrant and its potential to meaningfully improve outcomes across ER-positive early-stage and advanced breast cancer. The US FDA recently accepted the NDA for giredestrant in combination with everolimus for those with ESR1 -mutated, ER-positive advanced breast cancer based on the evERA results, with a decision expected in December 2026. Roche’s expanding giredestrant clinical development programme spans distinct treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible. Globally, 2.3 million people are diagnosed with breast cancer each year. 8 ER-positive breast cancer accounts for approximately 70% of breast cancer cases, and the majority are diagnosed in the early-stage. 9,10 Currently, up to a third of people eventually experience recurrence on or after adjuvant endocrine therapy treatment for early-stage breast cancer. 10-12 Additionally, many have to interrupt or stop treatment early due to safety or tolerability issues, thereby increasing the risk of death. 13,14 These limitations underscore the need for more effective and better-tolerated options that can enhance adherence and prevent or delay disease recurrence. About the lidERA Breast Cancer study lidERA Breast Cancer [ NCT04961996 ] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of adjuvant giredestrant versus standard-of-care endocrine therapy in people with medium- or high-risk stage I-III oestrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. 15 Over 4,100 patients were enrolled in the study. 15 The primary endpoint is invasive disease-free survival (iDFS) excluding unrelated cancers in other organs (second primary non-breast cancers). 15 Key secondary endpoints include overall survival, iDFS including second primary non-breast cancers, disease-free survival and safety. 15 About giredestrant Giredestrant is an investigational, oral, potent next-generation selective oestrogen receptor degrader and full antagonist. 16 Giredestrant is designed to block oestrogen from binding to the oestrogen receptor, triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells. 17 Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible: Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996 ) 15 Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340 ) 18 Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009 ) 19 Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748 ) 20 Giredestrant plus Phesgo® (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798 ) 21 About oestrogen receptor (ER)-positive breast cancer Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year.8 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type. 22 ER-positive breast cancer accounts for approximately 70% of breast cancer cases, and the majority are diagnosed in the early-stage.9 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth. 23 Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. 24 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. 24, 25 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives. 24, 25 About Roche in breast cancer Roche has been advancing breast cancer research for more than 30 years, and it continues to be a major focus of research and development. Our legacy began with the development of the first targeted therapy for human epidermal growth factor receptor 2-positive breast cancer, and we continue to push the boundaries of science to address the complexities of all breast cancer subtypes. By leveraging our dual expertise in pharmaceuticals and diagnostics, we are dedicated to providing tailored treatment approaches and improving outcomes for every patient, from early to advanced stages of the disease. Together with our partners, we are relentlessly pursuing a cure, as we strive for a future where no one dies from breast cancer. About Roche Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions. Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them. Genentech in the United States is a fully owned subsidiary in the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market. For more information, please visit . All trademarks used or mentioned in this release are protected by law. References [1] Bardia A, et al. Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial. Presented at: San Antonio Breast Cancer Symposium (SABCS); 2025 December 9-12; San Antonio, Texas, United States. #GS1-10. [2] Baum M, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359(9324):2131-9. [3] Thürlimann B, et al. A Comparison of Letrozole and Tamoxifen in Postmenopausal Women with Early Breast Cancer. N Engl J Med; 2005;353:2747-57. [4] F. Hoffmann‑La Roche Ltd. (2026) SEER Explorer All BCa by Stage. Data on file. [5] F. Hoffmann‑La Roche Ltd. (2026) Stage Distribution. Data on file. [6] F. Hoffmann‑La Roche Ltd. (2026) KREBS and TRM. Data on file. [7] F. Hoffmann‑La Roche Ltd. (2026). UK_CRUK_EDHub_IncidenceByStageRCRD_DataTable2026-01-08. Data on file. [8] World Health Organization. Breast Cancer [Internet; cited 2026 June]. Available from: [9] Kinslow C, et al. Prevalence of Estrogen Receptor Alpha (ESR1) Somatic Mutations in Breast Cancer. JNCI Cancer Spectrum; 2022;6(5):pkac060. [10] Shaughnessy J, et al. Real-world risk of recurrence and treatment outcomes with adjuvant endocrine therapy in patients with stage II-III HR+/HER2- early breast cancer. Breast. 2025;81:104437. [11] Pan H, et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. NEJM. 2017;377:1836–46. [12] Khatpe AS, et al. Nexus between PI3K/AKT and Estrogen Receptor Signaling in Breast Cancer. Cancers (Basel). 2021;13(3):369. [13] Hershman DL, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126:529–37. [14] Rosso R, et al. Adherence to Adjuvant Endocrine Therapy in Breast Cancer Patients. Curr Oncol. 2023;30(2):1461-72. [15] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2- Negative Early Breast Cancer (lidERA Breast Cancer) [Internet; cited 2026 June]. Available from: [16] Martin M, et al. Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase 2, randomised, open-label acelERA BC study. Presented at: ESMO Annual Meeting; 2022 September 9-13; Paris, France. Abstract #211MO. [17] Metcalfe C, et al. GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes. Presented at: SABCS; 2018 December 4-8; San Antonio, Texas, United States. Abstract #P5-04-07. [18] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With the Physician's Choice of Endocrine Therapy Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer) [Internet; cited 2026 June]. Available from: [19] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2- Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer) [Internet; cited 2026 June]. Available from: [20] ClinicalTrials.gov. A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/ 6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) [Internet; cited 2026 June]. Available from: [21] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer) [Internet; cited 2026 June]. Available from: . [22] World Health Organization. Cancer Today [Internet; cited 2026 June]. Available from: . [23] National Cancer Institute. Hormone Therapy for Breast Cancer [Internet; cited 2026 June]. Available from: [24] Hanker A, et al. Overcoming Endocrine Resistance in Breast Cancer. Canc Cell. 2020;37(4):496–513. [25] Başaran G, et al. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer. Cancer Treat Rev. 2018;63:144-55. Roche Global Media Relations Phone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhD Phone: +41 79 407 72 58 Lorena Corfas Phone: +41 79 568 24 95 Simon Goldsborough Phone: +44 797 32 72 915 Karsten Kleine Phone: +41 79 461 86 83 Kirti Pandey Phone: +41 79 398 38 53 Yvette Petillon Phone: +41 79 961 92 50 Dr Rebekka Schnell Phone: +41 79 205 27 03 Irène Stephan Phone: +41 79 377 83 75 Roche Investor Relations Dr Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr Sabine Borngräber Phone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr Birgit Masjost Phone: +41 61 68-84814 e-mail: birgit.masjost@roche.com Investor Relations North America Loren Kalm Phone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment Media&Investor Release lidERA FDA Filing Acceptance English