ALK Treatment
When you visit your oncologist it’s natural to have a lot of questions – and you have the right to ask as much or as little as you’d like. ALK Positive UK has put together a guide, ‘Good Practice from the Patients’ Perspective’, which includes a list of key questions you may wish to ask your oncologist, helping you to feel empowered and informed about your treatment.
Access the support PDF here:
All patients can ask for a second opinion regarding their diagnosis or treatment plan, either privately or within the NHS.
This is usually related to the treatment plans, rather than the diagnosis, and the second opinion will be from an oncologist.
Before asking for a second opinion, you should ask your oncologist or specialist nurse to go over anything you feel unsure about, like your treatment options. Your healthcare team will be happy to explain things, and sometimes there may be no need for a second opinion.
The NHS does not have to provide a second opinion, but you have the right to ask for one. Most doctors will be happy to refer you, and this will not have an impact on your patient-doctor relationship. You may ask for a second opinion in any NHS trust, regardless of where you live. Note that each trust and their clinicians have the right to accept or decline referrals for second opinions, often guided by the service capacity and volume of referrals.
The oncologist who will provide a second opinion will rely on a detailed referral letter and the copies of all relevant exams, such as biopsies, blood results or CT scans. Therefore, to proceed with a second opinion, a referral will be required, ideally from a medical professional currently involved with your care.
This referral is often from the current oncologist (at your request), but alternatively it may also be from your GP. A referral from the current oncologist is preferred, since the GP relies on the information passed on from the oncologist, and they may not have all your relevant test results. Some GPs may not feel they have enough information to request a second opinion on behalf of a patient. Sometimes the oncologist doing a second opinion may also need additional information, so it helps if they are directly in contact with your current oncology team.
Getting a second opinion will take time and it may involve travelling to a different hospital. That means it may delay your treatment which may affect your wellbeing. It is important to be open with your oncology team and discuss this.
A second opinion is not a transfer of care. After your second opinion, you may continue under your current oncologist or you may wish to ask for a transfer of care. A transfer of care needs to be formally accepted by the new oncologist and arranged between the current and the new medical teams to ensure there is no negative impact on your care.
Macmillan Cancer Support offers further advice on getting a second opinion: Getting a second opinion – Macmillan Cancer Support.
TKIs are the key treatment for ALK+ lung cancer. They are oral tablets which work by blocking the signalling pathway that the mutated ALK-fusion proteins are using to tell the cancer cell to grow and replicate.
The journey from the discovery of ALK rearrangements in NSCLC (non-small cell lung cancer) in 2007 to the first approval of a TKI in 2013 in the UK is a remarkable success story in medicine. Since then, advancements in medicine have made TKIs even more effective – and further developments are being made all the time.
The TKIs which are currently approved in the UK are:
It can be useful to think of TKIs in terms of a subway system. In ALK+ lung cancer, the fused ALK-EML4 gene creates mutated ALK-fusion proteins. The ALK-fusion proteins trigger messages, telling the cell to grow and replicate.
Each message can be thought of as a passenger on a subway train. The message travels towards the cell’s nucleus via a signalling pathway in the cell – or a subway line. TKIs work by blocking this pathway, so the message – or the train – has to stop. Eventually, though, the passenger realises that they can take another subway line to reach their same destination. In the same way, the tumour cell protein finds another signalling pathway that can be used to send the message.
Once the message reaches the nucleus – the structure in a centre of a cell which controls the cell’s behaviour – the cell is instructed to grow and multiply.
The video below illustrates this process.
Your oncologist will recommend a TKI based on these factors:
There are several things we don’t yet know. Currently, no trials compare second- and third-generation ALK inhibitors directly in a first-line setting. Therefore, we don’t have sufficient evidence to definitively say that any one TKI is superior to the others. There is also not enough evidence to support a specific sequencing strategy (the order in which the TKIs are used).
The flowchart below shows the order in which TKIs are currently given in the UK, according to guidance from NICE (the National Institute for Health and Care Excellence). Your oncology team will select a first-line treatment depending on your particular cancer and circumstances. If this treatment stops working, or needs to be stopped due to side effects, you will usually be given the second-line treatment as shown below.
(Flowchart last updated February 2025)
After some time, a TKI will stop working against the cancer. This happens because of mutations within the cancer cell.
Mutations are changes to the DNA of a cell which make it behave differently. In this case, the mutation allows the cancer cell to bypass the TKI and continue to grow and multiply.
These are the steps that might be taken if your cancer progresses while on a TKI treatment.
If your cancer progresses while on a TKI, you can often be moved on to another. The order in which TKIs are given depends on which TKI was used first. Your oncology team will consider your individual case and circumstances carefully when deciding the best steps to take.
If a tumour is growing in one/a few locations while the disease is otherwise under control (oligoprogressive disease), you may be given local treatment (mainly radiotherapy, or sometimes surgery) while continuing to take the same TKI.
Once a patient progresses on a third-generation ALK inhibitor, chemotherapy becomes the standard of care.
If your cancer progresses, a new biopsy is sometimes carried out on the growing or new tumour. This biopsy helps rule out whether the cancer has transformed to a different type of lung cancer. It may also open up opportunities for you to take part in clinical trials. However, your oncology team will always carefully weigh up the decision to perform a new biopsy, considering both the risks and potential benefits to you.
In early-stage ALK+ lung cancer, if the tumour can be removed by surgery (and surgery is suitable for the patient), surgery is usually carried out. This is sometimes accompanied by chemotherapy (either before or after the time of surgery).
However, in November 2024, NICE (the National Institute for Health and Care Excellence) approved the use of alectinib after surgery for early-stage ALK+ non-small cell lung cancer (in the UK).
This is because clinical trials showed that when patients were given alectinib after surgery, their cancer was less likely to return than if they were given chemotherapy after surgery (Wu et al., 2024).
Alectinib can be used as adjuvant treatment (treatment given after surgery) in adults with tumours staged as 1B to 3A, after the tumour has been completely resected (removed). It can be offered for up to two years with the aim of delaying or preventing the cancer from coming back. (NICE, 2024)
For tumours which cannot be removed by surgery, the standard treatment is chemoradiotherapy, a treatment which combines chemotherapy and radiotherapy.
Treatment for brain metastases generally consists of two different approaches:
There is no ‘one size fits all’ approach to how often and what type of regular tests are needed to monitor lung cancer after diagnosis.
Below is some general information about what your oncology team might recommend, depending on the stage of your cancer. You can learn more about cancer stages here.
Earlier stage lung cancer here refers to cancers which are staged between stage 1 and 3a. These cancers have not yet grown very big or spread too far, and tend to be treated with a ‘curative intent’ – that is, with treatments chosen to give the best chance of curing the cancer.
While there is no standard follow-up pathway, patients are usually monitored for at least 5 years after the curative treatment (for example, after surgery). A mix of CT scans and chest x-rays will be used during this time to check for anything of concern.
Check-ups will usually be between 3 and 6 months apart, and will often be more frequent in the first years after the treatment, then become less frequent over time if nothing concerning is found.
There is also no standard approach to including head scans as part of this monitoring. Some patients will be given occasional head scans if they are thought to be higher risk, for example those with stage 3 disease.
This refers to a cancer which is at stages 3b – 4, meaning that the cancer has spread significantly within the chest and/or beyond. These cancers tend to be treated with ‘palliative intent’: treatment which aims to control the cancer to help people live longer and more comfortably. The majority of ALK+ lung cancer cases are diagnosed at stage 4.
Patients with later stage ALK+ lung cancer are likely to be treated with ALK inhibitors following diagnosis, for as long as the treatment is working and any side effects are manageable.
While there is no standard follow-up, patients will often have a monthly clinical review, which may become less frequent over time depending on the side effects experienced. Patients will also usually be given a regular CT scan (most commonly every 3 months), which will normally be used to check the chest, abdomen and pelvis.
Other areas may be included in the regular scan, depending where the cancer is in the body. You are also likely to be given head scans, which your oncology team will discuss with you.
In this conversational video, lung cancer clinical nurse specialist Delyth McEntee speaks to Debra Montague, chair of ALK Positive UK, about her experiences with side effects from ALK treatment. The topics covered include:
Below are some of the side effects that can arise from the ALK targeted treatments currently funded by the National Institute for Health and Care Excellence (NICE) in the UK. These TKIs are crizotinib, alectinib, ceritinib, brigatinib and lorlatinib.
Please note that each treatment also has cautions and contraindications associated with its use. There may be reasons why a treatment is not suitable for you, for example if you have other medical conditions. Your oncology team will prescribe the best TKI for you based on your cancer and specific circumstances.
Many of the side effects reference increased or decreased levels of enzymes and other components found in your body. These changes can indicate that the medication is affecting areas of your body such as your liver or pancreas. Your oncology team will monitor these changes so they can take any additional steps needed.
If you experience side effects:
The most important thing to do is to speak to your oncology team. Here are some of the ways your team can support you with side effects:
In this video, clinical research nurse team leader Sharon Woolley talks about the importance of clinical trials in cancer. The topics covered include:
Clinical trials (often called clinical research) are extremely important in cancer care and treatment. Clinical trials aim to help us:
Many clinical trials have informed the current treatment for ALK+ lung cancer that we use today.
Clinical trials are designed in different ways, depending on what needs to be learned from them.
| Type of trial | Treatment details |
| Randomised controlled trial | Equal groups of randomly selected people receive different treatments or no treatments |
| Open label not randomised trial | Both the patients and those running the trial know which treatment trial participants are going to receive before the trial starts |
| Blind trial | The participants don’t know which type of treatment they’re receiving |
| Double blind trial | Neither the participants, nor those running the trial, know which treatment participants are receiving |
| Placebo controlled trial | One group in the trial is receiving a treatment, while another group isn’t. The participants don’t know which group they are in |
All new treatments have to go through several phases of clinical trials before they can be approved for use, to make sure they are safe for patients.
The phases of a trial are:
Phase 1 (early) trials measure areas such as side effects and dose - often for the first time - in small groups of people with cancer.
Phase 2 trials look at things like side effects, the effects of one treatment compared with another (or compared with no treatment) over several years in larger groups of people with cancer.
Phase 3 trials examine safety, the effectiveness of different doses and combinations, and patients’ quality of life on a much wider scale. These can involve thousands of people with cancer in several places, often internationally, and are usually randomised.
Phase 4 trials can sometimes be needed to monitor the effectiveness, safety and side effects in large and diverse populations.
Please be aware that the following links are current (as of December 2024), some may reside behind a paywall.
