New England Journal of Medicine publishes landmark phase III results for Roche’s Itovebi, showing more than doubling of progression-free survival in certain type of HR-positive advanced breast cancer
Roche announced the publication of phase III INAVO120 trial results for Itovebi in the New England Journal of Medicine. The Itovebi-based regimen showed significant benefits in HR-positive, HER2-negative breast cancer patients with PIK3CA mutations, reducing disease progression or death risk by 57% compared to standard treatment. The median progression-free survival improved to 15.0 months versus 7.3 months with palbociclib and fulvestrant alone. The FDA recently approved this combination as first-line treatment. The PIK3CA mutation affects approximately 40% of HR-positive metastatic breast cancers and is associated with poor prognosis.
Roche ha annunciato la pubblicazione dei risultati dello studio di fase III INAVO120 per Itovebi sul New England Journal of Medicine. Il regime basato su Itovebi ha mostrato benefici significativi nei pazienti con cancro al seno HR-positivo e HER2-negativo con mutazioni PIK3CA, riducendo il rischio di progressione della malattia o morte del 57% rispetto al trattamento standard. La mediana della sopravvivenza libera da progressione è migliorata a 15,0 mesi rispetto a 7,3 mesi con palbociclib e fulvestrant da soli. La FDA ha recentemente approvato questa combinazione come trattamento di prima linea. La mutazione PIK3CA colpisce circa il 40% dei tumori metastatici al seno HR-positivi ed è associata a una prognosi sfavorevole.
Roche anunció la publicación de los resultados del ensayo de fase III INAVO120 para Itovebi en el New England Journal of Medicine. El régimen basado en Itovebi mostró beneficios significativos en pacientes con cáncer de mama HR-positivo y HER2-negativo con mutaciones PIK3CA, reduciendo el riesgo de progresión de la enfermedad o muerte en un 57% en comparación con el tratamiento estándar. La mediana de supervivencia libre de progresión mejoró a 15,0 meses frente a 7,3 meses con palbociclib y fulvestrant solos. La FDA aprobó recientemente esta combinación como tratamiento de primera línea. La mutación PIK3CA afecta aproximadamente al 40% de los cánceres de mama metastásicos HR-positivos y está asociada con un mal pronóstico.
로슈가 이토베비의 III상 INAVO120 시험 결과를 New England Journal of Medicine에 발표했습니다. 이토베비 기반의 요법은 PIK3CA 변이가 있는 HR-양성, HER2-음성 유방암 환자에서 표준 치료에 비해 질병 진행 또는 사망 위험을 57% 감소시키는 유의미한 혜택을 보여주었습니다. 무진행 생존 중앙값이 15.0개월 대 7.3개월로 향상되었습니다. FDA는 최근 이 조합을 1차 치료로 승인했습니다. PIK3CA 변이는 HR-양성 전이성 유방암의 약 40%에 영향을 미치며, 이는 나쁜 예후와 관련이 있습니다.
Roche a annoncé la publication des résultats de l'essai de phase III INAVO120 pour Itovebi dans le New England Journal of Medicine. Le régime basé sur Itovebi a montré des avantages significatifs chez les patients atteints d'un cancer du sein HR-positif et HER2-négatif avec des mutations PIK3CA, réduisant le risque de progression de la maladie ou de décès de 57 % par rapport au traitement standard. La médiane de survie sans progression a été améliorée à 15,0 mois contre 7,3 mois avec le palbociclib et le fulvestrant seuls. La FDA a récemment approuvé cette combinaison comme traitement de première ligne. La mutation PIK3CA affecte environ 40 % des cancers du sein métastatiques HR-positifs et est associée à un mauvais pronostic.
Roche gab die Veröffentlichung der Ergebnisse der Phase-III-Studie INAVO120 für Itovebi im New England Journal of Medicine bekannt. Das Itovebi-basierte Regime zeigte signifikante Vorteile bei HR-positiven, HER2-negativen Brustkrebspatientinnen mit PIK3CA-Mutationen, indem das Risiko für Krankheitsprogression oder Tod im Vergleich zur Standardbehandlung um 57 % gesenkt wurde. Das mediane progressionsfreie Überleben verbesserte sich auf 15,0 Monate versus 7,3 Monate mit Palbociclib und Fulvestrant allein. Die FDA genehmigte kürzlich diese Kombination als Erstlinientherapie. Die PIK3CA-Mutation betrifft etwa 40 % der HR-positiven metastatischen Brustkrebse und ist mit einer schlechten Prognose verbunden.
- FDA approval secured for first-line treatment
- 57% reduction in disease progression or death risk
- More than doubled progression-free survival (15.0 vs 7.3 months)
- Positive trend in overall survival data (HR=0.64)
- Consistent benefits across all pre-specified subgroups
- Overall survival data still immature and pending further analysis
- ItovebiTM (inavolisib)-based regimen demonstrated a statistically significant and clinically meaningful benefit, reducing the risk of disease worsening or death by
57% compared with palbociclib and fulvestrant alone in the INAVO120 study1 - The U.S. FDA recently approved the Itovebi-based regimen as a first-line treatment for people with HR-positive, HER2-negative breast cancer with a PIK3CA mutation, one of the most commonly mutated genes in HR-positive disease2
Basel, 31 October 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that a detailed analysis of the positive phase III INAVO120 results, evaluating ItovebiTM (inavolisib) in combination with palbociclib (Ibrance®) and fulvestrant were published in the New England Journal of Medicine.1 The United States Food and Drug Administration (FDA) recently approved Itovebi in combination with palbociclib and fulvestrant, for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency.
“With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients,” said Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and one of the principal investigators of the INAVO120 study. “I’m confident this Itovebi-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis.”
Results showed the Itovebi-based regimen reduced the risk of disease worsening or death (progression-free survival [PFS]) by
“Publication of these phase III results in the New England Journal of Medicine further highlights the transformative potential of the Itovebi-based regimen,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This new treatment exemplifies our ambition to target specific disease pathways more effectively and improve outcomes in people with breast cancer, while also emphasising the importance of comprehensive testing for mutations like PIK3CA at the time of diagnosis.”
The PIK3CA mutation is found in approximately
Itovebi is currently being investigated in three company-sponsored phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations.6-8 We are exploring additional studies in breast cancer and other tumour types with the hope of bringing the benefit of this targeted therapy to more people with PIK3CA mutations and addressing patient unmet needs.
About the INAVO120 study
The INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.6
The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm.6 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause.6 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.6
Beyond INAVO120, Itovebi is currently being investigated in two additional company-sponsored phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:7,8
- in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 inhibitor and endocrine combination therapy (INAVO121; NCT05646862), and
- in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
About hormone receptor (HR)-positive breast cancer
HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately
About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of
helping as many people with the disease as possible. Our medicines, along with companion
diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.9,10
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045.
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References
[1] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. NEJM. 2024;391(17).
[2] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22:1002.
[3] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179.
[4] Princic N, et al. Abstract P1-18-18: PIK3CA mutation testing prevalence among post-menopausal (PM) women with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC) using real world data. Cancer Res. 2020;80(4):P1-18-18.
[5] Wales Cancer Network. PIK3CA-mutated breast cancer clinical guidance document [Internet; cited 2024 October]. Available from: https://executive.nhs.wales/functions/networks-and-planning/cancer/wcn-documents/mutated-breast-cancer-clinical-guidance-document//.
[6] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2024 October]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499.
[7] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2024 October]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862.
[8] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer [Internet; cited 2024 October]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239.
[9] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2024 October]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
[10] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696.
[11] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20.
[12] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10.
Dr. Jhaveri has financial interests related to Roche and Genentech.
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