IMFINZI® (durvalumab) perioperative regimen improved event-free survival and overall survival across muscle-invasive bladder cancer patients regardless of complete pathology response status in post-hoc exploratory analysis of NIAGARA Phase III trial
AstraZeneca's IMFINZI (durvalumab) demonstrated significant improvements in a post-hoc exploratory analysis of the NIAGARA Phase III trial for muscle-invasive bladder cancer (MIBC). The perioperative regimen, combining IMFINZI with neoadjuvant chemotherapy, showed improved event-free survival (EFS) and overall survival (OS) versus chemotherapy alone.
Key findings include:
- 42% risk reduction in disease progression for patients achieving pathologic complete response (pCR)
- 33% reduction in risk of distant metastases
- 31% reduction in risk of death specifically due to bladder cancer
- 10% improvement in pCR rate versus comparator arm
The treatment was generally well-tolerated with no new safety signals. IMFINZI received Priority Review in the US in December 2024, with regulatory applications under review in EU, Japan, and other countries.
IMFINZI di AstraZeneca (durvalumab) ha mostrato significativi miglioramenti in un'analisi esplorativa post-hoc dello studio di Fase III NIAGARA per il cancro della vescica muscolo-invasivo (MIBC). Il regime perioperatorio, che combina IMFINZI con la chemioterapia neoadiuvante, ha evidenziato un miglioramento della sopravvivenza libera da eventi (EFS) e della sopravvivenza globale (OS) rispetto alla chemioterapia da sola.
I principali risultati includono:
- Riduzione del rischio di progressione della malattia del 42% per i pazienti che raggiungono una risposta completa patologica (pCR)
- Riduzione del 33% del rischio di metastasi a distanza
- Riduzione del 31% del rischio di morte specificamente a causa del cancro della vescica
- Miglioramento del 10% del tasso di pCR rispetto al braccio comparatore
Il trattamento è stato generalmente ben tollerato, senza nuovi segnali di sicurezza. IMFINZI ha ricevuto la Revisione Prioritaria negli Stati Uniti a dicembre 2024, con domande regolatorie in fase di revisione in UE, Giappone e altri paesi.
IMFINZI de AstraZeneca (durvalumab) demostró mejoras significativas en un análisis exploratorio post-hoc del ensayo de Fase III NIAGARA para el cáncer de vejiga músculo-invasivo (MIBC). El régimen perioperatorio, que combina IMFINZI con quimioterapia neoadyuvante, mostró una mejoría en la supervivencia libre de eventos (EFS) y en la supervivencia global (OS) en comparación con la quimioterapia sola.
Los hallazgos clave incluyen:
- Reducción del riesgo de progresión de la enfermedad del 42% para los pacientes que lograron una respuesta completa patológica (pCR)
- Reducción del 33% en el riesgo de metástasis a distancia
- Reducción del 31% en el riesgo de muerte específicamente debido al cáncer de vejiga
- Mejora del 10% en la tasa de pCR frente al grupo comparador
El tratamiento fue generalmente bien tolerado, sin nuevas señales de seguridad. IMFINZI recibió Revisión Prioritaria en EE. UU. en diciembre de 2024, con aplicaciones regulatorias en revisión en la UE, Japón y otros países.
아스트라제네카의 IMFINZI (두르발루맙)는 근육 침습성 방광암 (MIBC)에 대한 NIAGARA 3상 시험의 후향적 탐색 분석에서 상당한 개선을 보여주었습니다. IMFINZI와 보조 화학요법을 결합한 수술 전 요법은 단독 화학요법에 비해 사건 발생 없는 생존율 (EFS) 및 전체 생존율 (OS)이 향상되었습니다.
주요 발견 사항은 다음과 같습니다:
- 병리학적 완전 반응 (pCR)을 달성한 환자에서 질병 진행 위험 42% 감소
- 원거리 전이 위험 33% 감소
- 방광암으로 인한 사망 위험 31% 감소
- 비교군에 비해 pCR 비율 10% 개선
치료는 일반적으로 잘 견뎌졌으며 새로운 안전성 신호는 없었습니다. IMFINZI는 2024년 12월 미국에서 우선 심사를 받았으며, EU, 일본 및 기타 국가에서 규제 신청이 검토 중입니다.
IMFINZI d'AstraZeneca (durvalumab) a montré des améliorations significatives dans une analyse exploratoire post-hoc de l'essai de Phase III NIAGARA pour le cancer de la vessie musculo-invasif (MIBC). Le régime périopératoire, combinant IMFINZI avec une chimiothérapie néoadjuvante, a montré une amélioration de la survie sans événement (EFS) et de la survie globale (OS) par rapport à la chimiothérapie seule.
Les résultats clés comprennent:
- Réduction de 42% du risque de progression de la maladie pour les patients atteignant une réponse complète pathologique (pCR)
- Réduction de 33% du risque de métastases à distance
- Réduction de 31% du risque de décès spécifiquement dû au cancer de la vessie
- Amélioration de 10% du taux de pCR par rapport au groupe comparateur
Le traitement a généralement été bien toléré, sans nouveaux signaux de sécurité. IMFINZI a reçu une Révision Prioritaire aux États-Unis en décembre 2024, avec des demandes réglementaires en cours d'examen dans l'UE, au Japon et dans d'autres pays.
IMFINZI von AstraZeneca (Durvalumab) zeigte signifikante Verbesserungen in einer post-hoc explorativen Analyse der NIAGARA Phase-III-Studie für muskelinvasiven Blasenkrebs (MIBC). Das perioperative Regime, das IMFINZI mit neoadjuvanter Chemotherapie kombiniert, zeigte eine verbesserte ereignisfreie Überlebensrate (EFS) und Gesamtüberlebensrate (OS) im Vergleich zur alleinigen Chemotherapie.
Wichtige Ergebnisse umfassen:
- 42% Risikominderung bei Krankheitsfortschritt für Patienten mit pathologischer kompletter Ansprechrate (pCR)
- 33% Risikominderung für Fernmetastasen
- 31% Risikominderung für Todesfälle spezifisch aufgrund von Blasenkrebs
- 10% Verbesserung der pCR-Rate im Vergleich zur Kontrollgruppe
Die Behandlung wurde im Allgemeinen gut vertragen, ohne neue Sicherheitsmeldungen. IMFINZI erhielt im Dezember 2024 in den USA eine Prioritätsprüfung, mit regulatorischen Anträgen, die in der EU, Japan und anderen Ländern geprüft werden.
- Significant 42% risk reduction in disease progression for pCR patients
- 33% reduction in risk of distant metastases
- 31% reduction in risk of death from bladder cancer
- 10% improvement in pathologic complete response rate
- Priority Review status granted in US
- None.
Insights
The NIAGARA Phase III trial results represent a significant advancement in muscle-invasive bladder cancer treatment, with several key implications for AstraZeneca's market position and future revenue potential:
The 33% reduction in distant metastases risk is particularly noteworthy, as metastatic disease typically results in significantly higher treatment costs and poorer outcomes. This improvement could translate into substantial healthcare cost savings and better patient outcomes, strengthening the economic argument for IMFINZI adoption.
The efficacy demonstrated across both pCR and non-pCR patients is crucial, as it indicates broader applicability of the treatment. The 42% risk reduction in pCR patients and 23% in non-pCR patients suggests robust clinical benefit regardless of initial response, potentially expanding the eligible patient population.
The Priority Review designation in the US, coupled with pending applications in the EU and Japan, positions IMFINZI for potential rapid market entry in major healthcare markets. The strong safety profile, with manageable and mostly low-grade immune-mediated adverse events, should support favorable regulatory decisions and subsequent physician adoption.
These results strengthen AstraZeneca's position in the immuno-oncology space, particularly in earlier-stage cancer treatment where the market opportunity is substantial. The perioperative approach represents a strategic expansion of IMFINZI's utility beyond its current indications, potentially establishing a new standard of care in MIBC treatment.
IMFINZI reduced the risk of distant metastases and death from bladder cancer vs. neoadjuvant chemotherapy alone
These new data were presented today at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in
In
The IMFINZI perioperative regimen also improved metastasis-free survival (MFS) and disease-specific survival (DSS), two secondary endpoints, versus the comparator arm in the intent-to-treat (ITT) population. This regimen reduced the risk of developing distant metastases or death by
Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “NIAGARA was the first Phase III trial of a perioperative immunotherapy regimen in muscle-invasive bladder cancer to show statistically significant and clinically meaningful improvements in event-free and overall survival. The 33 percent reduction in the risk of distant metastases, which are associated with a poorer prognosis, further reinforces the potential of perioperative IMFINZI to become a new standard of care in this setting.”
These new data build on findings presented at the European Society for Medical Oncology (ESMO) Congress and published in The New England Journal of Medicine which showed
Summary of exploratory post-hoc analysis:
|
Patients with pCR |
Patients without pCR |
ITT population |
|||
|
IMFINZI-
|
Neoadjuvant
|
IMFINZI-
|
Neoadjuvant
|
IMFINZI-
|
Neoadjuvant
|
pCRi |
||||||
pCR rate
|
- |
- |
- |
- |
37.3 |
27.5 |
p-valueii |
- |
- |
0.0005 |
|||
EFSi |
||||||
EFS rate, |
|
|||||
24 months |
92.1 |
85.8 | 53.3 | 49.5 | 67.8 | 59.8 |
(%) |
||||||
HR ( |
0.58 |
0.77 |
0.68 |
|||
CI) |
(0.33-1.00) |
(0.63-0.95) |
(0.56-0.82) |
|||
OSi |
||||||
OS rate, 24
|
95.5 |
91.1 |
74.1 |
68.9 |
82.2 |
75.2 |
HR ( |
0.72 |
0.84 |
0.75 |
|||
CI) |
(0.37-1.43) |
(0.66-1.07) |
(0.59-0.93) |
|||
i Data cut-off: April 29, 2024 |
||||||
ii Nominal p-value |
Summary of additional secondary endpoint outcomes (ITT):
|
IMFINZI-based regimen
|
Neoadjuvant chemotherapy
|
MFSi |
||
MFS rate, 24 months (%) |
75.1 |
65.1 |
Number of MFS events |
152 |
201 |
(%) |
(28.5) |
(37.9) |
Median MFS ( |
NRii |
NRii |
months) |
(NRii-NRii) |
(48.0-NRii) |
HR ( |
0.67
|
|
DSSi |
||
DSS rate, 24 months (%) |
89.2 |
82.2 |
Number of deaths due to |
85 |
114 |
bladder cancer (%) |
(15.9) |
(21.5) |
Median DSS ( |
NRii |
NRii |
months) |
(NRii-NRii) |
(NRii-NRii) |
HR ( |
0.69
|
|
i Data cut-off: April 29, 2024 |
||
ii NR, not reached |
IMFINZI was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding IMFINZI to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of IMFINZI, manageable and mostly low-grade.
Perioperative IMFINZI in combination with neoadjuvant chemotherapy was granted Priority Review in the US in December 2024 for the treatment of patients with MIBC. Regulatory applications are also currently under review in the European Union (EU),
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
-
IMFINZI as a Single Agent
-
In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was
2.4% (34/1414), including fatal (<0.1% ), and Grade 3-4 (0.4% ) adverse reactions. -
In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was
18.3% (87/475) in patients receiving IMFINZI and12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475),1.1% were fatal and2.7% were Grade 3 adverse reactions. -
The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was
14% (37/262) in patients receiving IMFINZI and6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262),0.4% had a fatal adverse reaction and2.7% had Grade 3 adverse reactions. - The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
-
In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was
-
IMFINZI with IMJUDO
-
Immune‑mediated pneumonitis occurred in
1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3% ) and Grade 3 (0.2% ) adverse reactions.
-
Immune‑mediated pneumonitis occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated pneumonitis occurred in
3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5% ), and Grade 3 (1% ) adverse reactions.
-
Immune-mediated pneumonitis occurred in
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
-
IMFINZI as a Single Agent
-
Immune-mediated colitis occurred in
2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1% ) and Grade 3 (0.4% ) adverse reactions.
-
Immune-mediated colitis occurred in
-
IMFINZI with IMJUDO
-
Immune‑mediated colitis or diarrhea occurred in
6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6% ) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
-
Immune‑mediated colitis or diarrhea occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated colitis occurred in
6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2% ) and Grade 3 (2.5% ) adverse reactions. Intestinal perforation and large intestine perforation were reported in0.1% of patients.
-
Immune-mediated colitis occurred in
Immune-Mediated Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.
-
IMFINZI as a Single Agent
-
Immune-mediated hepatitis occurred in
2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2% ), Grade 4 (0.3% ) and Grade 3 (1.4% ) adverse reactions.
-
Immune-mediated hepatitis occurred in
-
IMFINZI with IMJUDO
-
Immune‑mediated hepatitis occurred in
7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8% ), Grade 4 (0.3% ) and Grade 3 (4.1% ) adverse reactions.
-
Immune‑mediated hepatitis occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated hepatitis occurred in
3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3% ), Grade 4 (0.5% ), and Grade 3 (2% ) adverse reactions.
-
Immune-mediated hepatitis occurred in
Immune-Mediated Endocrinopathies
-
Adrenal Insufficiency: IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
-
IMFINZI as a Single Agent
-
Immune-mediated adrenal insufficiency occurred in
0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1% ) adverse reactions.
-
Immune-mediated adrenal insufficiency occurred in
-
IMFINZI with IMJUDO
-
Immune-mediated adrenal insufficiency occurred in
1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3% ) adverse reactions.
-
Immune-mediated adrenal insufficiency occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated adrenal insufficiency occurred in
2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8% ) adverse reactions.
-
Immune-mediated adrenal insufficiency occurred in
-
IMFINZI as a Single Agent
-
Hypophysitis: IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated.
-
IMFINZI as a Single Agent
-
Grade 3 hypophysitis/hypopituitarism occurred in <
0.1% (1/1889) of patients who received IMFINZI.
-
Grade 3 hypophysitis/hypopituitarism occurred in <
-
IMFINZI with IMJUDO
-
Immune-mediated hypophysitis/hypopituitarism occurred in
1% (4/388) of patients receiving IMFINZI and IMJUDO.
-
Immune-mediated hypophysitis/hypopituitarism occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated hypophysitis occurred in
1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5% ) adverse reactions.
-
Immune-mediated hypophysitis occurred in
-
IMFINZI as a Single Agent
-
Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
-
IMFINZI as a Single Agent
-
Immune-mediated thyroiditis occurred in
0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1% ) adverse reactions. -
Immune-mediated hyperthyroidism occurred in
2.1% (39/1889) of patients receiving IMFINZI. -
Immune-mediated hypothyroidism occurred in
8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1% ) adverse reactions.
-
Immune-mediated thyroiditis occurred in
-
IMFINZI with IMJUDO
-
Immune-mediated thyroiditis occurred in
1.5% (6/388) of patients receiving IMFINZI and IMJUDO. -
Immune-mediated hyperthyroidism occurred in
4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3% ) adverse reactions. -
Immune-mediated hypothyroidism occurred in
11% (42/388) of patients receiving IMFINZI and IMJUDO.
-
Immune-mediated thyroiditis occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated thyroiditis occurred in
1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. -
Immune-mediated hyperthyroidism occurred in
5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2% ) adverse reactions. -
Immune-mediated hypothyroidism occurred in
8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5% ) adverse reactions.
-
Immune-mediated thyroiditis occurred in
-
IMFINZI with Carboplatin and Paclitaxel
-
Immune-mediated hypothyroidism occurred in
14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.
-
Immune-mediated hypothyroidism occurred in
-
IMFINZI as a Single Agent
-
Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated.
-
INFINZI as a Single Agent
-
Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <
0.1% (1/1889) of patients receiving IMFINZI.
-
Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <
-
IMFINZI with IMJUDO
-
Two patients (
0.5% , 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
-
Two patients (
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated Type 1 diabetes mellitus occurred in
0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3% ) adverse reactions.
-
Immune-mediated Type 1 diabetes mellitus occurred in
-
INFINZI as a Single Agent
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
-
IMFINZI as a Single Agent
-
Immune-mediated nephritis occurred in
0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1% ) adverse reactions.
-
Immune-mediated nephritis occurred in
-
IMFINZI with IMJUDO
-
Immune-mediated nephritis occurred in
1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5% ) adverse reactions.
-
Immune-mediated nephritis occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated nephritis occurred in
0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2% ) adverse reactions.
-
Immune-mediated nephritis occurred in
Immune-Mediated Dermatology Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.
-
IMFINZI as a Single Agent
-
Immune-mediated rash or dermatitis occurred in
1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4% ) adverse reactions.
-
Immune-mediated rash or dermatitis occurred in
-
IMFINZI with IMJUDO
-
Immune-mediated rash or dermatitis occurred in
4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3% ) and Grade 3 (1.5% ) adverse reactions.
-
Immune-mediated rash or dermatitis occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Immune-mediated rash or dermatitis occurred in
7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3% ) adverse reactions.
-
Immune-mediated rash or dermatitis occurred in
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in
Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than
- Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
- Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism.
- Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.
-
IMFINZI as a Single Agent
-
Infusion-related reactions occurred in
2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3% ) adverse reactions.
-
Infusion-related reactions occurred in
-
IMFINZI with IMJUDO
-
Infusion-related reactions occurred in
2.6% (10/388) of patients receiving IMFINZI and IMJUDO.
-
Infusion-related reactions occurred in
-
IMFINZI with IMJUDO and Platinum-Based Chemotherapy
-
Infusion-related reactions occurred in
2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3% ) adverse reactions.
-
Infusion-related reactions occurred in
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.
Adverse Reactions
Unresectable Stage III NSCLC
-
In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥
20% ) were cough (40% ), fatigue (34% ), pneumonitis or radiation pneumonitis (34% ), upper respiratory tract infections (26% ), dyspnea (25% ), and rash (23% ). The most common Grade 3 or 4 adverse reactions (≥3% ) were pneumonia (7% ) and pneumonitis/radiation pneumonitis (3.4% ).
-
In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in
15% of patients in the IMFINZI arm. Serious adverse reactions occurred in29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2% ) were pneumonitis or radiation pneumonitis (7% ) and pneumonia (6% ). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms.
Resectable NSCLC
-
In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥
20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. -
In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in
6.7% of patients. Serious adverse reactions occurred in21% of patients. The most frequent (≥1% ) serious adverse reactions were pneumonia (2.7% ), anemia (1.5% ), myelosuppression (1.5% ), vomiting (1.2% ), neutropenia (1% ), and acute kidney injury (1% ). Fatal adverse reactions occurred in2% of patients, including death due to COVID-19 pneumonia (0.5% ), sepsis (0.5% ), myocarditis (0.2% ), decreased appetite (0.2% ), hemoptysis (0.2% ), and death not otherwise specified (0.2% ). Of the 401 IMFINZI treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment,1.7% (n=7) and1% (n=4), respectively, did not receive surgery due to adverse reactions. -
In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in
8% of patients. Serious adverse reactions occurred in13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9% ), pneumonitis (1.1% ), and COVID-19 (1.1% ). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm.
Metastatic NSCLC
-
In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥
20% of patients) were nausea (42% ), fatigue (36% ), musculoskeletal pain (29% ), decreased appetite (28% ), rash (27% ), and diarrhea (22% ). -
In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in
17% of patients. Serious adverse reactions occurred in44% of patients, with the most frequent serious adverse reactions reported in at least2% of patients being pneumonia (11% ), anemia (5% ), diarrhea (2.4% ), thrombocytopenia (2.4% ), pyrexia (2.4% ), and febrile neutropenia (2.1% ). Fatal adverse reactions occurred in a total of4.2% of patients.
Limited-stage Small Cell Lung Cancer
-
In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥
20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38% ), and fatigue (21% ). The most common Grade 3 or 4 adverse reactions (≥3% ) were pneumonitis or radiation pneumonitis and pneumonia. -
In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in
16% of the patients receiving IMFINZI. Serious adverse reactions occurred in30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12% ), and pneumonia (5% ). Fatal adverse reactions occurred in2.7% of patients who received IMFINZI including pneumonia (1.5% ), cardiac failure, encephalopathy and pneumonitis (0.4% each).
Extensive-stage Small Cell Lung Cancer
-
In patients with extensive-stage SCLC in the
CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20% ) were nausea (34% ), fatigue/asthenia (32% ), and alopecia (31% ). The most common Grade 3 or 4 adverse reaction (≥3% ) was fatigue/asthenia (3.4% ). -
In patients with extensive-stage SCLC in the
CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least1% of patients were febrile neutropenia (4.5% ), pneumonia (2.3% ), anemia (1.9% ), pancytopenia (1.5% ), pneumonitis (1.1% ), and COPD (1.1% ). Fatal adverse reactions occurred in4.9% of patients receiving IMFINZI plus chemotherapy.
Locally Advanced or Metastatic Biliary Tract Cancers
-
In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥
20% of patients) were fatigue (42% ), nausea (40% ), constipation (32% ), decreased appetite (26% ), abdominal pain (24% ), rash (23% ), and pyrexia (20% ). -
In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in
6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least2% of patients were cholangitis (7% ), pyrexia (3.8% ), anemia (3.6% ), sepsis (3.3% ) and acute kidney injury (2.4% ). Fatal adverse reactions occurred in3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).
Unresectable Hepatocellular Carcinoma
-
In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥
20% of patients) were rash (32% ), diarrhea (27% ), fatigue (26% ), pruritus (23% ), musculoskeletal pain (22% ), and abdominal pain (20% ). -
In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in
41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6% ), diarrhea (4% ), sepsis (2.1% ), pneumonia (2.1% ), rash (1.5% ), vomiting (1.3% ), acute kidney injury (1.3% ), and anemia (1.3% ). Fatal adverse reactions occurred in8% of patients who received IMFINZI and IMJUDO, including death (1% ), hemorrhage intracranial (0.5% ), cardiac arrest (0.5% ), pneumonitis (0.5% ), hepatic failure (0.5% ), and immune-mediated hepatitis (0.5% ). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in14% of patients.
Primary advanced or Recurrent dMMR Endometrial Cancer
-
In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >
20% of patients) were peripheral neuropathy (61% ), musculoskeletal pain (59% ), nausea (59% ), alopecia (52% ), fatigue (41% ), abdominal pain (39% ), constipation (39% ), rash (39% ), decreased magnesium (36% ), increased ALT (32% ), increased AST (30% ), diarrhea (27% ), vomiting (27% ), cough (27% ), decreased potassium (25% ), dyspnea (25% ), headache (23% ), increased alkaline phosphatase (20% ), and decreased appetite (18% ). The most common Grade 3 or 4 adverse reactions (≥3% ) were constipation (4.5% ) and fatigue (4.5% ). -
In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in
11% of patients. Serious adverse reactions occurred in30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4% ) were constipation (4.5% ) and rash (4.5% ).
The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.
You may report side effects related to AstraZeneca products.
Notes
Muscle-invasive bladder cancer
Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.1 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.2 Approximately one in four patients with bladder cancer has evidence of the tumor invading the muscle wall of the bladder (without distant metastases), known as MIBC.3-4
In MIBC, a curative-intent setting, approximately 117,000 patients are treated with the current standard of care, which includes neoadjuvant chemotherapy and radical cystectomy.5-6 However, even after cystectomy, approximately
The trial is being conducted at 192 centers across 22 countries including in
IMFINZI
IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses.
IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO® (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.
In addition to its indications in lung cancers, IMFINZI is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in
IMFINZI is also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by IMFINZI monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, IMFINZI plus chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer, and IMFINZI plus chemotherapy followed by IMFINZI alone is approved for patients with dMMR disease. In
Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumors.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in
References |
|
US-98018 Last Updated 2/25
View source version on businesswire.com: https://www.businesswire.com/news/home/20250214771953/en/
Media
Fiona Cookson +1 212 814 3923
Chelsea Tressler +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
Source: AstraZeneca