Anaplastic lymphoma kinase (ALK) inhibitors

Alectinib

• Capsules 150mg

Notes

1. NICE TA536: Alectinib (Alecensa) is recommended, within its marketing authorisation, as an option for untreated anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults. It is recommended only if the company provides alectinib according to the commercial arrangement (August 2018).

Ceritinib

• Tablets 150mg

Notes

1. NICE TA395: Ceritinib (Zykadia) is recommended, within its marketing authorisation, as an option for treating advanced anaplastic lymphoma kinase positive non-small-cell lung cancer in adults who have previously had crizotinib. It is recommended only if the company provides it with the discount agreed in the patient access scheme (June 2016).
2. NICE TA500: Ceritinib (Zykadia) is recommended, within its marketing authorisation, as an option for untreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer in adults, only if the company provides it with the discount agreed in the patient access scheme (January 2018).

Lorlatinib

• Tablets 25mg, 100mg

Notes

1. NICE TA628: Lorlatinib (Lorviqua) is recommended, within its marketing authorisation, as an option for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults (May 2020), whose disease has progressed after:
   1. alectinib or ceritinib as the first ALK tyrosine kinase inhibitor or
   2. crizotinib and at least 1 other ALK tyrosine kinase inhibitor.
   3. It is recommended only if the company provides lorlatinib according to the commercial arrangement.
2. NICE TA909: Lorlatinib (Lorviqua) is not recommended, within its marketing authorisation, for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults who have not had an ALK inhibitor (July 2023).

BCR-ABL tyrosine kinase inhibitors

MHRA Drug Safety Update (May 2016): BCR-ABL tyrosine kinase inhibitors: risk of hepatitis B reactivation. BCR-ABL tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) are used in the treatment of chronic myeloid leukaemia or Philadelphia chromosome positive acute lymphoblastic leukaemia

1. Test patients for infection with hepatitis B virus (HBV) before starting treatment with BCR-ABL tyrosine kinase inhibitors
2. Consult experts in liver disease and in the treatment of HBV before starting treatment with BCR-ABL tyrosine kinase inhibitors in patients with positive HBV serology (including those with active disease) and for patients who test positive for HBV during treatment
3. Patients who are carriers of HBV who require treatment with BCR-ABL tyrosine kinase inhibitors should be closely monitored for signs and symptoms of active HBV infection throughout treatment and for several months after stopping

Asciminib

• Tablets 20mg, 40mg

Notes

1. NICE TA813: Asciminib (Scemblix) is recommended, within its marketing authorisation, as an option for treating chronic-phase Philadelphia chromosome-positive chronic myeloid leukaemia without a T315I mutation after 2 or more tyrosine kinase inhibitors in adults. It is recommended only if the company provides asciminib according to the commercial arrangement (August 2022).

Bosutinib

• Tablets 100mg, 500mg

Notes

1. NICE TA401: Bosutinib (Bosulif) is recommended as an option, within its marketing authorisation, for chronic, accelerated and blast phase Philadelphia chromosome positive chronic myeloid leukaemia in adults (August 2016), only when:
   1. they have previously had 1 or more tyrosine kinase inhibitor and
   2. imatinib, nilotinib and dasatinib are not appropriate and
   3. the company provides bosutinib with the discount agreed in the patient access scheme (as revised in 2016).

Dasatinib

• Tablets 20mg, 50mg, 80mg, 100mg, 140mg

Notes

1. NICE TA425: Dasatinib, nilotinib and high-dose imatinib for treating imatinib-resistant or intolerant chronic myeloid leukaemia (December 2016):
   1. Dasatinib (Sprycel), is recommended as an option for treating only chronic- or accelerated-phase Philadelphia-chromosome-positive chronic myeloid leukaemia in adults if they cannot have imatinib, or their disease is imatinib-resistant, and the company provides dasatinib with the discount agreed in the relevant patient access scheme (December 2016).
2. NICE TA426: Dasatinib, nilotinib and imatinib for untreated chronic myeloid leukaemia (December 2016):
   1. Dasatinib (Sprycel) is recommended, within its marketing authorisation, as an option for untreated chronic-phase Philadelphia-chromosome-positive chronic myeloid leukaemia in adults only if the company provides dasatinib with the discount agreed in the relevant patient access scheme.

Imatinib

• Tablets 100mg, 400mg

Notes

1. NICE TA326: Imatinib (Glivec) is recommended as an option as adjuvant treatment for up to 3 years for adults who are at high risk of relapse after surgery for KIT (CD117)‑positive gastrointestinal stromal tumours, as defined by the Miettinen 2006 criteria (November 2014).
2. NICE TA70: Imatinib is recommended as an option for the treatment of people with Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) who initially present in the accelerated phase or with blast crisis. Additionally, imatinib is recommended as an option for people who present in the chronic phase and then progress to the accelerated phase or blast crisis if they have not received imatinib previously (October 2003: updated January 2016).
3. NICE TA86: Imatinib for the treatment of unresectable and/or metastatic gastro-intestinal stromal tumours (October 2004: updated November 2010):
   1. Imatinib treatment at 400 mg/day is recommended as first-line management of people with KIT (CD117)-positive unresectable and/or KIT (CD117)-positive metastatic gastro-intestinal stromal tumours (GISTs).
   2. Continuation with imatinib therapy is recommended only if a response to initial treatment is achieved within 12 weeks.
   3. Responders should be assessed at intervals of approximately 12 weeks thereafter. Continuation of treatment is recommended at 400 mg/day until the tumour ceases to respond.
   4. An increase in the dose of imatinib is not recommended for people receiving imatinib who develop progressive disease after initially responding.
   5. The use of imatinib should be supervised by cancer specialists with experience in the management of people with unresectable and/or metastatic GISTs.
4. NICE TA426: Dasatinib, nilotinib and imatinib for untreated chronic myeloid leukaemia (December 2016):
   1. Imatinib (Glivec) is recommended as an option for untreated, chronic-phase Philadelphia-chromosome-positive chronic myeloid leukaemia in adults.
5. NICE TA209: Imatinib at 600 or 800mg/day is not recommended for people with unresectable and/or metastatic gastrointestinal stromal tumours whose disease has progressed after treatment with 400 mg/day imatinib (November 2010).
6. NICE TA425: Dasatinib, nilotinib and high-dose imatinib for treating imatinib-resistant or intolerant chronic myeloid leukaemia (December 2016).
   1. High-dose imatinib (that is, 600mg in the chronic phase or 800mg in the accelerated and blast-crisis phases) is not recommended for treating Philadelphia-chromosome-positive chronic myeloid leukaemia in adults whose disease is imatinib-resistant.

Nilotinib

• Capsules 150mg, 200mg

Notes

1. NICE TA425: Dasatinib, nilotinib and high-dose imatinib for treating imatinib-resistant or intolerant chronic myeloid leukaemia (December 2016):
   1. Nilotinib (Tasigna) is recommended as an option for treating only chronic- or accelerated-phase Philadelphia-chromosome-positive chronic myeloid leukaemia in adults if they cannot have imatinib, or their disease is imatinib-resistant, and the company provides dasatinib with the discount agreed in the relevant patient access scheme (December 2016).
2. NICE TA426: Dasatinib, nilotinib and imatinib for untreated chronic myeloid leukaemia (December 2016):
   1. Nilotinib (Tasigna) is recommended as an option for untreated chronic-phase Philadelphia-chromosome-positive chronic myeloid leukaemia in adults.

Ponatinib

• Tablets 15mg, 30mg, 45mg

Notes

1. NICE TA451: Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia (June 2017):
   1. Ponatinib (Iclusig) is recommended, within its marketing authorisation, as an option for treating chronic‑, accelerated‑ or blast‑phase chronic myeloid leukaemia in adults, only when the criteria of the NICE TA are met.
   2. Ponatinib (Iclusig) is recommended, within its marketing authorisation, as an option for treating Philadelphia-chromosome-positive acute lymphoblastic leukaemia in adults, only when the criteria of the NICE TA are met.
2. MHRA Drug Safety Update (December 2014): Ponatinib (Iclusig): risk of vascular occlusive events.
3. MHRA Drug Safety Update (April 2017): Ponatinib (Iclusig): risk of vascular occlusive events – updated advice on possible dose reduction.
4. MHRA Drug Safety Update (October 2018): Ponatinib (Iclusig): reports of posterior reversible encephalopathy syndrome.
5. MHRA Drug Safety Update (July 2020): Systemically administered VEGF pathway inhibitors: risk of aneurysm and artery dissection
   1. Before initiating a systemic VEGF pathway inhibitor, carefully consider the risk of aneurysm and artery dissection in patients with risk factors (see Drug Safety Update for a list of risk factors).
   2. In patients who receive a systemic VEGF pathway inhibitor, reduce as far as possible any modifiable risk factors such as smoking and hypertension.
   3. Monitor patients for and treat hypertension in accordance with recommendations in the SPC (click here).

Bruton tyrosine kinase (BTK) inhibitors

Acalabrutinib

• Capsules 100mg

Notes

1. NICE TA689: Acalabrutinib for treating chronic lymphocytic leukaemia (April 2021)
   1. Acalabrutinib (Calquence) as monotherapy is recommended as an option for untreated chronic lymphocytic leukaemia (CLL) in adults, only if:
      1. there is a 17p deletion or TP53 mutation, or
      2. there is no 17p deletion or TP53 mutation, and fludarabine plus cyclophosphamide and rituximab (FCR), or bendamustine plus rituximab (BR) is unsuitable, and
      3. the company provides the drug according to the commercial arrangement.
   2. Acalabrutinib (Calquence) as monotherapy is recommended, within its marketing authorisation, as an option for previously treated CLL in adults.
      1. It is recommended only if the company provides the drug according to the commercial arrangement.

Ibrutinib

• Tablets 140mg
  

Notes

1. NICE TA429: Ibrutinib (Imbruvica) alone is recommended within its marketing authorisation as an option for treating chronic lymphocytic leukaemia in adults (January 2017):
   1. who have had at least 1 prior therapy or
   2. who have a 17p deletion or TP53 mutation, and in whom chemo-immunotherapy is unsuitable and
   3. only when the company provides ibrutinib with the discount agreed in the patient access scheme.
2. NICE TA502: Ibrutinib (Imbruvica) is recommended as an option for treating relapsed or refractory mantle cell lymphoma only if they have had only 1 previous line of therapy and the company provides ibrutinib with the discount agreed in the commercial access agreement with NHS England (January 2018).
3. NICE TA891: Ibrutinib (​Imbruvica​) plus venetoclax ​is recommended​, within its marketing authorisation, as an option for untreated chronic lymphocytic leukaemia (CLL) in adults, only if the companies provide both drugs according to the commercial arrangements (May 2023).
4. NICE TA795: Ibrutinib (Imbruvica) is not recommended, within its marketing authorisation, for treating Waldenstrom's macroglobulinaemia in adults who have had at least 1 previous therapy (June 2022).
5. MHRA Drug Safety Update (August 2017): Ibrutinib (Imbruvica): reports of ventricular tachyarrhythmia; risk of hepatitis B reactivation and of opportunistic infections.
6. Healthcare professional letter (November 2022): Imbruvica (ibrutinib): New risk minimisation measures, including dose modification recommendations, due to the increased risk for serious cardiac events.

Zanubrutinib

• Capsules 80mg

Notes

1. NICE TA833: Zanubrutinib (Brukinsa) is recommended as an option for treating Waldenstrom's macroglobulinaemia in adults who have had at least 1 treatment (October 2022), only if:
   1. bendamustine plus rituxumab is also suitable and
   2. the company provides it according to the commercial arrangement.
2. NICE TA931: Zanubrutinib (Brukinsa) is recommended as an option for treating chronic lymphocytic leukaemia (CLL) in adults, only if the company provides it according to the commercial arrangement (November 2023). It is only recommended if the CLL is:
   1. untreated and
      1. there is a 17p deletion or tumour protein 53 (TP53) mutation or
      2. there is no 17p deletion or TP53 mutation, and fludarabine plus cyclophosphamide and rituximab (FCR), or bendamustine plus rituximab (BR) is unsuitable, or
   2. relapsed or refractory.