1 Summary

The policy provides details of the arrangements for managing treatment breaks for people receiving systemic anti-cancer therapy/ies (SACT).

The policy replaces the previous guidance on treatment breaks which was suspended during the COVID-19 pandemic and replaced by the process described in COVID-19 rapid guideline: delivery of systemic anti-cancer treatments, National Institute for Health and Care Excellence (NICE) guideline [NG161].

For the purpose of the policy, the term SACT is used instead of chemotherapy and refers to traditional cytotoxic medicines, targeted therapies, monoclonal antibodies, antibody drug conjugates, cancer immunotherapy (IO) and enzyme/hormonal treatments with anti-cancer actions.

A treatment break may be planned or unplanned. The policy intention is to set out when SACT can and cannot be resumed with NHS England funding after an unplanned extended treatment break. See sections 1.1 and 1.2 for definitions of panned and unplanned treatment breaks.

Restarting treatment after a break from SACT is an option for people of all ages (children, teenagers, young adults, and adults) where clinical circumstances meet the inclusion criteria in the policy:

• If a person has an unplanned treatment break of less than or equal to six weeks (or 12 weeks in the case of immunotherapy) beyond the ending of the last treatment cycle the person can restart treatment without a treatment break request form being submitted by their oncology or haematology clinician.
• If a person has an unplanned treatment break of greater than six weeks (or 12 weeks in the case of immunotherapy) beyond the ending of the last treatment cycle their oncology or haematology clinician will have to submit a treatment break request and comply with the requirements of the policy in order to resume the same NHS England funded SACT treatment.
• For treatment breaks during which disease progression has occurred, restarting the same SACT treatment is not approved under the policy. The specific exceptions to this requirement are defined in the policy.
• The policy defines the specific circumstances where a request for funding following a break in treatment is not required or not appropriate.

Restarting treatment after a planned treatment break is not approved under the policy. Where an intermittent treatment schedule is specifically commissioned, (see section 1.1) treatment can be restarted without a treatment break application.

Where sufficient published clinical evidence is available, NHS England will consider requests (submitted via the clinical policy proposal process) for changes to clinical commissioning policies for treatment breaks in other medicines/clinical scenarios.

1.1 Planned intermittent scheduled treatment breaks

Planned intermittent scheduled SACT occurs when the SACT is prescribed and administered with a specific timeframe of being ‘on’ treatment, followed by an ‘off’ treatment time resumed within the expected timeframe for that regimen; eg three months on treatment followed by three months off treatment.

Planned treatment breaks must only be used when supported by robust clinical evidence and are in line with NICE technology appraisal (TA) or an NHS England commissioning policy and specified in the relevant NHS England treatment criteria.

1.2 Unplanned treatment breaks

An unplanned treatment break occurs when the administration has to be stopped and the recognised treatment schedule is interrupted.

An unplanned treatment break can be to allow for drug related toxicities to improve or to enable the person to undergo/recover from surgery or radiotherapy. Unplanned treatment breaks may also occur for reasons unrelated to the SACT such as a treatment for a concurrent illness or major trauma.

If a person has an unplanned treatment break of greater than six weeks (or 12 weeks in the case of immunotherapy) beyond the ending of the last treatment cycle their oncology or haematology clinician will have to submit a treatment break application form and comply with the requirements of this policy to resume the same NHS funded SACT treatment.

Unplanned treatment breaks less than this time limit (6/12 weeks) do not require a treatment break form to be submitted.

1.3 Resumption of NHS England funding requests

A treatment break form to request resumption of NHS funding is not required for breaks of less than six weeks (for SACT excluding immunotherapy) or 12 weeks (for immunotherapy) beyond the last day of the last treatment cycle.

The end of the last treatment cycle, which is equivalent to or defined as the date the next cycle of treatment would have started.

When an unplanned treatment break is greater than six weeks or 12 weeks (for immunotherapy) beyond the ending of the last treatment cycle, a treatment break form must be submitted to request resumption of NHS England SACT funding. The request must meet all the criteria described in the policy.

Certain SACT interventions are exempt from the need for clinicians to complete and submit a treatment break form on the prior approval system to resume NHS England funded SACT treatment. These are detailed in section 6 of the policy.

The prior approval system is used to submit the treatment break form (see section 5). In creating the policy, NHS England has reviewed the clinical pathway for SACT, including the use of the prior approval system by prescribers for approval of initial funding requests and to manage the treatment break process.

2 Equality statement

Promoting equality and addressing health inequalities are at the heart of NHS England’s values. Throughout the development of the policies and processes cited in this document, we have:

• given due regard to the need to eliminate discrimination, harassment and victimisation, to advance equality of opportunity, and to foster good relations between people who share a relevant protected characteristic (as cited under the Equality Act 2010) and those who do not share it
• given regard to the need to reduce inequalities between people in access to, and outcomes from healthcare services and to ensure services are provided in an integrated way where this might reduce health inequalities.

3 Plain language summary

3.1 About treatment schedules for systemic anti-cancer therapy and immunotherapy

There are many ways to treat cancer, which includes several different types of cancer medicines. These are collectively termed systemic anti-cancer therapies (SACT).

SACT is used for several reasons, including to cure the cancer without the need for any other treatment: this is called curative treatment.

It can be used prior to other treatment (neo-adjuvant), such as surgery or radiotherapy; or, following other cancer treatments, adjuvant SACT can be used to eradicate any hidden cancer cells that might remain in your body.

Your clinicians may recommend SACT to help ease any signs or symptoms of your cancer. This is termed palliative treatment.

Cancer medicines need to be taken in specific ways, which are called regimens. Some regimens can be for a specified timeframe, such as a three-month course after which treatment stops. Other regimens are continuous until the cancer stops responding to the treatment regimen or the person is unable to cope with the side effects of the medicines.

Some regimens will include planned, intermittent treatment, eg three months on the regimen treatment followed by a treatment break from SACT.

The medical doctor (oncologist/haematologist) will advise you regarding treatment breaks specific to the SACT regimen you are taking.

3.2 Treatment breaks

The use of planned breaks in treatment as part of an intermittent schedule, eg three months on treatment followed by three months off treatment must only be used when it is in line with published guidance from a NICE TA or part of an NHS England clinical commissioning policy.

The treatment break policy supports people who need to take an unplanned break from treatment, eg to allow recovery from drug related side effects and interruptions to treatment as a result of the need for surgery and/or radiotherapy or treatment for a new illness or a medical emergency unrelated to the cancer.

3.3 What we have decided

NHS England has carefully reviewed the need for the treatment break policy. The policy position has been updated, having considered previous guidance and current clinical evidence.

The guidance remains in place to ensure cancer medicines or combinations of cancer medicines are correctly prescribed according to each individual medicine’s summary of product characteristics (SmPC) and the commissioning decision for the use of that medicine(s) in a specific group of cancer patients.

The SmPC is the document that describes how the medicine is licensed to be used.

4 Rationale for the treatment break process

There is robust evidence in support of the non-inferiority of elective planned treatment breaks of standard cytotoxic SACT compared with continuous treatment, in several clinical areas, eg metastatic large bowel cancer.

However, such evidence does not exist for most targeted therapies which have completely different mechanisms of action when compared with standard cytotoxic SACT.

Targeted therapies are systemic therapy medicines with a targeted mode of action (eg medicine names ending in ‘-ibs’, ‘-mabs’, ‘-stats’). Additional examples include abiraterone, enzalutamide, apalutamide or IOs.

(Please note – this is not an exhaustive list; any type of medicine with a targeted mode of action is included within this definition.)

As part of the drug’s marketing authorisation and NICE appraisal for use in the NHS, targeted therapies are usually licensed to be used on a continuous basis until disease progression or loss of clinical benefit occurs.

In certain circumstances, targeted therapies may have specifically been licensed for a fixed duration and accordingly appraised by NICE.

For treatment breaks during which disease progression has occurred, restarting the same SACT treatment is not approved under the policy, apart from exemptions listed in section 7.

A treatment break is defined as a break in the standard treatment schedule of greater than six weeks beyond the expected cycle length or 12 weeks in the case of IO medicines and without there being any clinical evidence to suggest progression of the cancer or loss of the clinical benefit expected from the medicine.

Immunotherapy can cause systemic immune mediated side effects which take longer to resolve than side effects from all other SACT. Therefore, the policy allows an additional six weeks (ie up to 12 weeks) to enable recovery from these side effects.

Nonetheless, it is anticipated that recovery from surgery or toxicity would, in the majority of people (see exemptions below), occur within the six or 12-week windows.

Therefore, any breaks lasting longer than this will require submission of a prior authorisation request to ensure the extended treatment break was unplanned and fits within the principles of the policy.

5 Process to be followed

The following paragraphs describe the process and factors that should be considered when making a request to fund resumption of SACT following a break in treatment.

All applications for resumption of NHS England funding for SACT following a break in treatment must be submitted via the prior approval system. Initial contact and queries should be via the Cancer Drugs Fund (CDF) team at england.cdf@nhs.net.

5.1 Inclusion criteria

Requests to fund resumption of SACT following a break in treatment should be made via this process when all the following conditions apply:

• The person is receiving SACT with a targeted mode of action.

And:

• There has been a break in treatment of more than six weeks beyond the expected cycle length.

The exceptions to this six-week rule are:

• with systemic immune therapies (ie currently atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab and pembrolizumab plus other therapies in future) where people can have a break in treatment of up to 12 weeks beyond the expected cycle length.

Or:

• where a different maximum duration of treatment break is explicitly documented in the NHS England funding approval criteria for that specific medicine, on the relevant NHS England SACT funded treatment pathway or in the NICE TA guidance.

In the case of a targeted therapy that does not require a prior approval form to be completed, eg trastuzumab for breast cancer, the clinician will need to choose the ‘Not Listed – No Prior Approval’ and enter the medicine details manually on the treatment break form.

5.2 Exclusion criteria

The person must not have started any other SACT treatment for the same malignancy during the treatment break to be eligible to restart treatment.

However, it is acceptable for surgical treatment or radiotherapy for symptom management of the same malignancy to be performed during a treatment break (see Section 6 regarding synchronous cancers).

Treatment must be restarted as soon as clinically appropriate after a treatment break. People are not eligible to restart treatment (under this part of the policy) if the break in treatment has continued for four weeks or more beyond recovery from surgery/radiotherapy or resolution of toxicity to grade 1 or less.

This is to ensure patients restart the same SACT treatment they were taking prior to the treatment break without delay.

6 Where funding requests following a break in treatment are not required or not appropriate

A request for funding ongoing treatment is not required when any of the conditions noted below apply:

• People who are only receiving standard cytotoxic SACT unless the need for treatment break approval is specified in the NHS England clinical treatment criteria.
• People with a synchronous primary cancer diagnosis (ie a new type of cancer unrelated to the initial diagnosis) may stop the original treatment in order to receive treatment for the new cancer and restart the treatment for the original cancer without the need to complete a treatment break provided it is clinically appropriate to do so.
• Where the treatment break is a result of recovery from surgery or toxicity in the following specific scenarios, a break can occur without this process being followed but only where the disease has not been thought to have progressed during the break:
  • Interval debulking in ovarian and gastric cancer (eg bevacizumab containing chemotherapy in ovarian cancer)
  • Recovery from liver resection or primary tumour resection in metastatic colorectal cancer (eg cetuximab/panitumumab containing SACT regimens as per their commissioning criteria).
  • Recovery from cardiac toxicity (eg with HER2 targeted agents).
• Re-initiation of treatment with tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib or nilotinib, first or second line in people with Philadelphia positive chronic phase chronic myeloid leukaemia (CML) who have discontinued treatment in an attempt to achieve treatment-free remission.
  • If disease recurs (usually defined as confirmed BCR-ABL/ABL PCR ratio of >0.1%) the originally administered TKI can be restarted without having to submit a prior notification approval request.
• Re-initiation of treatment with checkpoint inhibitors (immunotherapy) for metastatic melanoma following two years of treatment to achieve disease control then interrupted until disease progression at which time the same treatment may be restarted on completion of the relevant continuation forms on the prior approval system.

7 Exceptions to the need to demonstrate lack of progression

For treatment breaks during which disease progression has occurred, restarting the same SACT treatment is not approved under the policy, apart from exceptions below.

A treatment break form is required for people receiving cetuximab or panitumumab in combination with cytotoxic medicines (oxaliplatin/ irinotecan/ 5-fluorouracil) in first line metastatic colorectal cancer if their unplanned treatment break is greater than six weeks beyond the expected cycle length.

However, there is an exception to the need to demonstrate a lack of progression before restarting treatment where the conditions below are met:

• People can restart the same cetuximab/panitumumab regimen if there are signs of progression only if their clinician considers it is biologically plausible that they will regain disease control and respond to a continuation of the same treatment.
• In order for consideration as a treatment break, the cytotoxic medicines given as part of the cetuximab/panitumumab regimen have to remain exactly the same as those administered prior to the treatment break.
  • (Please note: dose modifications permitted in the regimen protocol are allowed.)
  • If the cytotoxic medicines are changed, this represents a change in line of treatment rather than a treatment break.
• People who have had an extended break (longer than eight weeks) for recovery from toxicity. However, people whose cancer has progressed after a break of less than eight weeks (from the end of their last cycle) are deemed to have progressive disease and cannot restart the cetuximab/panitumumab regimen. They must proceed to second line therapy.
• The person must have their response to the same cetuximab or panitumumab chemotherapy regimen assessed within three months of restarting the treatment.
  • If there is evidence they are not responding to treatment and have progressive disease, the cetuximab or panitumumab regimen treatment must be discontinued.
• The person must restart treatment in a timely fashion, no later than four weeks after they have recovered from their surgery/radiotherapy or from date of resolution of toxicity to grade 1 or less.
• The treatment break must not be part of a planned intermittent treatment strategy, if there is evidence of use of treatment breaks to facilitate a planned intermittent treatment strategy the treatment break request will be declined.
  • Cetuximab and panitumumab are licensed for continuous use only. The use of a planned intermittent treatment strategy involving cetuximab or panitumumab with cytotoxic medicines is not commissioned for NHS use in England.
• All other requirements for a treatment break are met.

8 Criteria for reviewing treatment break requests

The NHS England regional cancer pharmacists, on behalf of the CDF Team, assess all applications (treatment break forms) against the policy for resumption of funding following a treatment break.

The application for continued NHS funding will either be approved or declined on the prior notification system.

Alternatively, the pharmacist may request further information before a decision can be made. The requesting clinician will receive an email via the prior approval system to notify them that a decision has been made or additional information has been requested.

The applications are assessed against the following criteria:

• A treatment break is not a treatment strategy planned in advance. There may be exceptional personal circumstances that justify the need for a treatment break.
  • However, advice should be sought from the NHS England regional cancer pharmacists before the treatment break commences.
  • Pre-approval of a request for a treatment break is not possible due to the potential for changes in clinical circumstances.
• An unplanned extended treatment break has occurred in reaction to unforeseen events (eg longer than expected recovery from surgery or toxicity or medical emergency i.e. major trauma, concurrent disease needing immediate treatment).
• The person’s cancer is not considered to have progressed during the break from treatment (noting the exceptions listed above).
• That the clinical circumstances of application are within the scope of the policy.

Applicants will be notified that their request has been unable to be considered if it falls outside the scope of the treatment break request policy and will, where appropriate, be given advice on further options, eg the individual funding request (IFR) process.

9 Links and updates to other policies

This document updates the interim guidance on treatment breaks that was included in:

• Previous guidance on treatment breaks that was in place pre COVID-19 pandemic, as outlined in the Specialised Commissioning Provider Letter and circular, reference SSC1918, issued on 04/09/2018.
• NICE/ NHS England and Improvement joint guideline NG161 ‘COVID-19 rapid guideline: delivery of systemic anticancer treatments’ https://www.nice.org.uk/guidance/ng161.

This document also links to the individual SACT regimen treatment criteria for use of cancer medicines which translates NICE and NHS England clinical policy recommendations into a clinical guide as to use in practice.

These treatment criteria can be found on the national CDF list at https://www.england.nhs.uk/cancer/cdf/cancer-drugs-fund-list/ or on the application form(s) on the prior approval system.

Each individual treatment criteria indicates if this policy will apply to the specific individual SACT regimen.

10 Implementation

Providers will need to ensure that any cancer medicine treatment break approved through this process is charged to the correct commissioner.

• Charges for cancer medicines/indications currently funded within the CDF should be submitted to the CDF.
• Charges for cancer medicines drugs/indications funded within routine commissioning should be submitted appropriately.

11 Governance arrangements

Provider organisations treating people with SACT will be required to assure itself that internal governance arrangements are in place to ensure clinical staff are aware of the requirements of the policy. NHS England may ask for assurance of the internal governance process.

Provider organisations must register all people prescribed SACT using prior approval system and ensure monitoring arrangements are in place to demonstrate compliance against the treatment criteria for each medicine /regimen indication.

12 Mechanism for funding

NHS England fund SACT treatments through the CDF and specialised commissioning.

13 Date of review

The policy will be reviewed when information is received which indicates that the policy requires revision.

If a review is needed due to a new evidence base then a new preliminary policy proposal needs to be submitted by contacting england.CET@nhs.net.

14 Definitions

Adjuvant

Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back.

CDF – cancer drugs fund

A source of funding which allows earlier access to cancer medicines in England via managed access arrangements, while further evidence is collected to address clinical uncertainty.

NHS England and NICE work in partnership with pharmaceutical companies to address uncertainty about the effectiveness of new cancer treatments.

Additional data gathered through the CDF helps NICE to decide whether a new treatment should be routinely funded on the NHS.

Cytotoxic medicines

(Sometimes known as antineoplastics) – a group of medicines that contain chemicals which are toxic to cells, preventing their replication or growth, and so are used to treat cancer.

HER2

A protein involved in normal cell growth.

HER2 may be made in larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body.

Checking the amount of HER2 on some types of cancer cells may help plan treatment.

IFR – individual funding request

An individual funding request can be made by a clinician treating you if they believe that your clinical circumstances are exceptional, and you may receive benefit from a treatment or service that is not routinely offered by the NHS.

The IFR route is how that funding is applied for.

Intermittent schedule

When a medicine is prescribed and taken for a set period of time with a break in treatment, followed by a resumption in treatment, eg three months of taking SACT followed by three months of break from taking SACT. The same SACT regimen resumed immediately after the three month ‘off’ period.

Neo adjuvant

Treatment given as a first step to shrink a tumour before the main treatment.

Planned treatment break

Another term for an intermittent treatment schedule – see above.

Targeted therapies

Systemic therapy medicines with a targeted mode of action to find and attack specific aspects of the cancer cell that helps the abnormal cells to grow.

These include drug names ending in ‘-ibs’, ‘-mabs’, ‘-stats’; other examples include abiraterone, enzalutamide, apalutamide.

Some types of targeted therapy are also an immunotherapy.

TKI – tyrosine kinase inhibitors

A substance that blocks the action of enzymes called tyrosine kinases.

Tyrosine kinases are a part of many cell functions, including cell signalling, growth, and division. These enzymes may be too active or found at high levels in some types of cancer cells and blocking them may help keep cancer cells from growing.

Some TKIs are used to treat cancer. They are a type of targeted therapy.

Unplanned treatment break

Any break in SACT being taken which is not part of an intermittent schedule, irrespective of the reason for the break.