Cancer diagnosis is hard but many survivors go on to have fulfilling lives. Even late-stage cancer does not necessarily spell doom. New medications are being evaluated, and there are a range of treatment choices available for all stages of cancer today. Scientific breakthroughs continue to be made in cancer research so there is hope!
Do Not panic! You are not alone. Of course, it can feel isolating as everyone has a unique cancer journey.
It is common to experience confusion and have lots of questions regarding your diagnosis, including treatment options and the implications of the diagnosis on your career and personal life.
Do not believe it if someone tells you that you may have caused your own cancer. There is no data that identifies any recognised cause of ROS1+ cancer. It’s vital to not look back, and instead the focus should be on living well and getting the cancer under control. Biologically, it’s not associated with tobacco usage too. While its unknown what the actual causes are, there are some breadcrumbs. They are usually seen in polluted environments. Exposure to diesel and charcoal particles plus wood burner fumes is also a tentative link. These are all scientific hypotheses though, rather than causative factors – and as forementioned it’s not a productive use of time to try and play the blame game.
Searching for cancer information can help you educate yourself and make better treatment decisions. But online cancer data are out of date, especially for rare cancers like ROS1 positive cancer. Prognosis for ROS1 cancer is improving. For example, the American Lung Association's 2022 State of Lung Cancer report indicated that five-year survival rates for those diagnosed with lung cancer have increased by 22% in the last five years. And there is progress in the five-year survival rate for other primary cancers as well. In short, cancer survival rates are always improving as knowledge advances and more treatment options become available.
The positive news is that ROS1 positive cancer cannot be passed down to your offspring. An unknown cause has resulted in your cells proliferating uncontrollably. In 99% of lung cancer cases, they are not inheritable particularly ROS1 positive cancer.
Stage 4 ROS1 positive cancer, is an advanced cancer. Stage 4 cancer occurs when the disease has progressed from the one part of the body to other organs of the body.
Treatment options for Stage 4 cancer includes; targeted therapies, chemotherapy, radiation, surgery and immunotherapy. Sometimes, a combination of one or two or more treatment options are used. At Stage IV, the cancer is deemed non-curable so the aim of the treatment is to prolong life expectancy and improve quality of life.
For adenocarcinoma, ROS1 tyrosine kinase inhibitors (TKIs) are superior to conventional chemotherapy in terms of both efficacy and tolerability. Chemical mediators (enzymes) known as tyrosine kinases are inhibited by Tyrosine kinase inhibitors (TKIs). Blocking tyrosine kinases prevents the cell from developing and proliferating, as they are responsible for transmitting growth signals to cells. Cancer growth blockers can inhibit one type of tyrosine kinase or multiple types. TKIs are often beneficial in patients who have previously had chemotherapy.
In the UK, for adenocarcinoma, there are 2 TKIs that have been approved by NICE to date for the treatment of ROS1 positive cancer: Crizotinib (brand name Xalkori) and Entrectinib (brand name Rozlytrek) . These come in pill form and are taken orally.
Although your specific treatment plan may differ, the following is a high-level overview of treatment options for ROS1 cancer.
Typically, during the first few months of treatment with the TKI, the majority of tumour shrinking takes place. For patients who are unable to tolerate a particular TKI during the initial therapy phase due to severe adverse side effects, it may be possible to switch to a different TKI.
Depending whether you have metastasis to the brain, either Crizotinib or Entrectinib will be prescribed. If you have one or more metastasised tumour(s) in the brain, your doctor may complement the treatment with targeted radiotherapy such as Stereotactic radiosurgery (SRS), Cyberknife or Gammaknife. Entrectininb hits hard on NTRK (neurotrophic tyrosine receptor kinase) so the patient may experience many side effects.
It’s important to know around 20% of patients ROS1 people do not develop a mutation ever.
The progression of the cancer is likely to develop with time in 80% of the cases, and the TKI may no longer be effective. At that stage, the cancer has developed a different mutation.
Your doctor may do a tissue or liquid biopsy again to identify why your medication is no longer working. Depending on the resistance mechanism identified, your doctor may recommend different treatment options.
It is a drug developed by Pfizer. It is effective on L2000V S1986F/L2000V mutations. It’s important to note that its lack of availability is not a major issue though. Resistance to first line drugs is usually due to G2032R mutation, and Lorlatinib also doesn’t agree with this so there might be limited uptake for it as a second line treatment.
It is however it is better at crossing the blood brain barrier, than earlier generation TKIs (Crizotinib and Entrectinib), so if progression is only occurring in the brain but not elsewhere it would be a useful drug, but Stereotactic Radio Surgery (SRS) is also a very good option here. If chemotherapy or other treatment options isn’t advisable due to other health issues, you can request the use of Lorlatininb on compassionate grounds. It is subject to approval by Pfizer.
It was developed by Turning Point Therapeutics which was then bought out by Bristol Myers Squibb. Repotrectinib is a potent inhibitor of ROS1, NTRK and also G2032R. As it harder than NTRK than entrectinib so it has many neuro side effects. This drug was subject to Phase 3 trials in the UK but hasn’t been approved by NICE yet.
It is manufactured by AnHeart Therapeutics. It is similar to Repotrectinib, but doesn’t hit NTRK as hard, so has less neuro side effects. It seems to have activity in the brain, as well as at G2032R, L2026M, L1951R, S1986F mutations. This drug hasn’t been approved by NICE.
ROS1 experts generally recommend against immunotherapy for Stage IV ROS1 lung cancer patients as it is often ineffective and could cause side effects that prevent a patient from taking a TKI as the next treatment option.
The side effects of ROS1 TKIs a patient experiences differ from person to person, but knowing what to anticipate may help you feel empowered and prepared.
The typical daily dosage to start with Crizotinib is 500 mg and Entrectinib is 600 mg, though it is not unusual to have doses reduced to manage side effects. Your doctor may prescribe medication to deal with the side effects. Typical side effects experienced by patients are listed below (not an exhaustive list):
1. Nausea and Vomiting
2. Diarrhoea
3. Constipation
4. Edema (swelling of arms, hands, feet, and legs)
5. Burning Oesophagus (sometimes experienced as reflux)
6. Fatigue or Tiredness
7. Brain Fog or Forgetfulness
8. Slower Heart Rate
9. Visual Disturbances
10. Difficulty Swallowing
11. Low Protein Levels
12. Low Iron Levels
13. Weight Gain
14. Taste Changes
15. Dizziness
16. Neuropathy (numbness or tingling, usually in hands and/or feet)
17. Skin Problems
18. Problems with muscles, connective tissue and bones
19. High Cholesterol (common with lorlatinib)
20. Liver Problems (can happen on crizotinib, entrectinib, or lorlatinib)
21. Low Testosterone, or Low T, in Men (primarily crizotinib)
22. Elevated Creatinine
Please note that the above listed side effects are not the only side effects that you may experience. Please consult your doctor to manage side effects more effectively.
Clinical trials are a type of research that studies new tests and treatments and evaluates their effects on human health outcomes. Cancer clinical trials determine the safety and effectiveness of cancer treatments in humans under supervision of trained researchers and medical professionals.
There are 4 phases of biomedical clinical trials:
Due to the rarity of ROS1 lung cancer, there are currently no clinical trials beyond Phase II.
You can find information on clinicaltrials,gov where you can search for ongoing trials in the UK.
If there are no clinical trials in the UK then you may consider going abroad to join a clinical trial, especially within Europe. However, this is subject to local requirements and may not always be possible (but it has been done a few times now)
We recently had a Nuvalent trial (NVL-520 for ROS1) although it is not showing up on the NICE website. It is the latest trial in the UK. There is Taletrectinib trial which is ongoing in Europe.
Joining a clinical trial is subject to specific eligibility criteria defined by the study as well as availability as places are limited.
You should consult your doctor if you wish to participate in a clinical trial. Your doctor will check against the eligibility criteria and assist with your enrolment in the clinical trial for you.
If your current TKI stops working, it will be worth exploring clinical trials in Europe. Please consult your doctor.
Simply receiving a cancer diagnosis is sufficient grounds to seek a second opinion. Most individuals don’t think twice about shopping around before buying a car, upgrading their home, or making another large investment. Before making treatment decisions based on a cancer diagnosis, it might be beneficial, if not crucial, to get a second opinion.
Numerous healthcare providers are not yet acquainted with ROS1+ cancer, as cancer research is undergoing rapid advancements.
You may wish to seek the advice of a consultant who has experience in treating numerous ROS1+ cancer cases and is engaged in ROS1 research if you have inquiries regarding the optimal next course of action for your ROS1+ cancer. Legally, no one has the right to a second opinion, but most of the time, people are not turned down for one. We can provide a list of known doctors. Please look at this link to see our clinical advice team who have knowledge and experience in treating in ROS1 patients.
Treatment for metastatic cancer may manage the disease for a while, but it cannot kill the cancer completely and, hence, does not cure it. There is usually another treatment option to attempt if the first one does not work. On occasion, the cancer can be active, and on other occasions, it may go into partial remission. A wide variety of treatments are often employed, either singly, in a combination, or in a specific order. Please consult your doctor about how to get the best possible treatment option for you.
We have compiled a set of Norms and Standards to assist you in navigating your cancer journey more effectively. They are not rules, but they might be seen as best practices for getting the most out of your treatment.
Your emotional well-being will take a toll to some degree if you get a cancer diagnosis. This could not only affect your own mental health, but also that of your loved ones and carers. Feelings of isolation, sadness, anxiety, and pain during and after cancer treatment are common. It is crucial to recognise these changes and get help when you need it.
If you are undergoing distress due to your cancer diagnosis then please let your doctor know about it. You may need professional help to deal with the situation.
Some of the tips to deal with this situation at your own level are listed below:
Discuss your experiences with others. It can be beneficial to be informed that your emotions are not uncommon, as it can alleviate feelings of isolation.
You can join our ROS1ders UK Facebook group and join other carers and patients.
In the UK, people with cancer can get financial assistance from a variety of sources, including their employer (if they work), government benefits such as Personal Independence Payment (PIP), Universal Credit, or Housing Benefit, their pension provider, or insurance company.
Please check this page to check if you can get help with finances: https://www.cancerresearchuk.org/
