PATIENT SPOTLIGHT: Xavier Chen, Paris, France
Xavier Chen has a very interesting story and treatment history which we thought many ALKies worldwide would be interested in reading. We interviewed him about his background, his journey, and all the things that he has learned along the way that he would want other ALK patients to know.
1. Tell us a little about your background - personal and professional - and your journey with ALK+ lung cancer so far.
I am a 61-year-old French citizen of Chinese origin, now living in Paris. Before my diagnosis, I was living in Chiangmai, a northern city of Thailand, in semi-retirement after a very fulfilling career successively in the French Foreign Service, International Energy Agency (IEA), global energy companies BP and Equinor, and Chinese energy company ENN. Before COVID, I spent 17 years in Beijing where I worked for the aforementioned companies as senior executive. I am also the founder and president of the Beijing Energy Club which is very vocal in promoting clean energy transition.
When COVID-19 was about to break out at the beginning of 2020, I left China to settle down in Chiangmai, where I have properties. I was in excellent health, living a very healthy life, surrounded by the greens, playing golf every week, while working online as part-time consultant for a few companies and organizations.
In early 2022, I felt a little discomfort in the left side of my chest. It pushed me to do a general health check at the local Ram Hospital. I used to do it every year but due to COVID, I hadn’t done it since 2019. It was this health check, on the 8th of February, 2022, that showed a 5 cm shadow on the X-ray which was confirmed in the following days as the stage IV ALK-positive NSCLC, with metastases to the liver, lymph nodes, and bones. I decided to come back to France for treatment.
I must say that I was very lucky to be diagnosed in Thailand, as the medical team there was very efficient. Within two weeks, every needed step for the initial diagnosis, including the biopsy, histopathological analysis, MRI, PET scan, etc. was done in good quality. So, when I flew back to France for consultation with my oncologists, they had everything they needed. This allowed me to start my first TKI, Alectinib, immediately, on the 4th of March. Four weeks from initial diagnosis to treatment - that’s very good speed.
2. Did Alectinib work well? Since then, what other treatments have you received?
Alectinib worked wonderfully in the beginning. My PET scan three months later, in June 2022, showed that all metastatic lesions were gone and the primary tumor size was reduced by half, but in September my first CT scan showed progression in the primary tumor, and the follow-up PET scan confirmed this and also showed a new lesion on the T12 vertebra. Since there were only two spots – the primary tumor and the T12 lesion, my oncologist suggested treating T12 with stereotactic body radiation therapy (SBRT) and the primary site with radiofrequency ablation (RFA) while keeping me on Alectinib.
The SBRT and RFA were very successful, but the cancer did not stop there. The next PET scan in December 2022 showed progression with new lesions in my mediastinal and abdominal lymph nodes. Furthermore, an MRI showed a new 8 mm lesion in the brain. My oncologist concluded that Alectinib was not working and that I needed to switch to Lorlatinib.
It's worth mentioning that during the RFA procedure they also took the opportunity to take a few samples of my tumor and send them for analysis. The reports came back confirming it was still NSCLC, ALK-positive, TP53-positive, PDL-1 at 65%, and without a MET amplification.
So, on the 21st December, 2022, I switched from Alectinib to Lorlatinib, hoping it would work while I enjoyed the Christmas holidays with my family. However, a PET scan in January 2023 showed more lesions in the body, and the MRI showed that the brain lesion had grown from 8 mm to 12.5 mm. My oncologist concluded that Lorlatinib was not working either and that I needed to start chemotherapy, while using brain SBRT (CyberKnife) to treat the brain lesion.
So, I started chemo on the 25th of January, 2023, and had the brain SBRT on 4th of February. The chemo was planned for 4 cycles with three weeks in between, with full dose of Cisplatin, Alimta (Permetrexed), and Avastin (Bevacizumab, an angiogenesis inhibitor), to be followed by maintenance chemo every 3 weeks with Alimta and Avastin, but, for the first chemo, Avastin was dropped due to interference with the forthcoming brain SBRT, and, starting from the 2nd cycle, Cisplatin was dropped and replaced by Carboplatin due to renal damage concerns. The maintenance cycles were mainly with Alimta only, as I often had other problems that prevented the use of Avastin. In total, I had 8 chemo sessions, 4 full doses, 4 maintenance chemo treatments, mainly with only Alimta, with the last session on the 7th of July. This interview reminds me that, out of my 8 chemo sessions, I missed Avastin 4 times. This could be a key factor for the failure of this first chemo line.
After the 4 full-dose chemo sessions, a PET scan showed there were 5 spots lit up, all lymph nodes, 4 in the mediastinal region and 1 in the abdominal area. My oncologist consulted the Medical Committee and decided to irradiate those in the mediastinal region with radiotherapy, while continuing the maintenance chemo every three weeks.
15 rounds of radiotherapy were done from the 13th of June to the 3rd of July, but in the end, they not only failed to kill the cancer cells, but they also caused a 3 cm ulcer in my esophagus! It was so painful that I could not even swallow my own saliva. I decided to go back to Thailand in mid-July, when my esophagitis was at its worst, because it's hard to find good services in Europe over the summer. In Thailand, an esophago-gastroscopy was immediately arranged, biopsy was taken from the ulcer, and CMV (cytomegalovirus) was found, and I was hospitalized for a week to receive antiviral drugs.
The big disappointment was that, when I came back to France at the end of August 2023 for my regular check-up and oncologist consultation, the PET scan showed cancer progression with many more lymph nodes affected. Luckily, the MRI showed nothing to worry about in the brain. My oncologist concluded that this first line of chemo was not working, and that, given my high PDL-1 expression, it would be worth it to try the combination of 2nd line chemo plus immunotherapy.
So, on the 21st of September, 2023, I received the first infusion of Carboplatin, Taxol (Paclitaxel, which works differently from Permetrexed), and Keytruda (Pembrolizumab, an anti-PD-1 inhibitor). This time, 4 cycles of these full-dose drugs were planned, and, if successful, they would be followed by immunotherapy (Keytruda) alone, every 6 weeks. A mid-term check in November showed very encouraging results with many bright spots shown on the precious PET scan disappearing, but a few new spots showing up.
The final verdict came when I had completed all four cycles plus one Keytruda alone infusion: my PET scan on the 23rd January 2024 showed significant progression in the lymph nodes with new lesions in the neck area and in the lower right lobe. The hope for immunotherapy to work was broken, and my oncologist suggested that I rechallenge with Lorlatinib while going through the pre-selection process for a few clinical trials. So, I am again on Lorlatinib now, and I hope it works this time.
So, you see, over the past two years, I have tried most of the advanced cancer treatment options: TKIs, chemotherapy, RFA surgery, SBRT, CyberKnife, radiotherapy, immunotherapy, and I have learned a lot.
I am happy to say that, despite the heavy treatment and the side effects, I am still in good shape, both physically and mentally.
3. Obviously, you went through a lot over the past two years. You mentioned the esophageal ulcer caused by the radiotherapy that made you suffer a lot. Have you experienced other major side effects with all these treatments?
Yes, I also had severe sore skin in the abdominal and chest area shortly after the RFA procedure in November 2022. This was because the procedure requires a large needle to penetrate my back to reach the tumor in the lung, so this punch damaged nerves on the way. The pain lasted for a month before it gradually went away.
I went to the emergency room twice last year due to infection by Gram-negative bacteria through my chemo port, which they removed and reinstalled three weeks later.
I tolerated the 2nd line of chemo plus immunotherapy treatment relatively well. The major side effects were caused by Taxol. My hair started to fall out significantly two weeks after my Taxol infusion, so I had to shave my head. But my hair started to grow back a month after the last Taxol infusion. I almost have all my hair back now, and the hair is much softer than before. Another side effect from Taxol is numbness in my toes. It started 1.5 month after the last Taxol infusion. It is only in the toes, not fingers. It was very severe, and I still haven’t recovered from it.
When I was on Alectinib or Lorlatinib, I also had side effects like skin rash, fatigue, constipation, neuropathy, etc., but compared to those of TKI, side effects from RFA, chemotherapy, and radiotherapy could be more serious. One lesson I learned from all these is that we the patients need to actively manage the side effects ourselves. Many doctors focus on killing the cancer cells but ignore the side effects that could also take our life.
4. You have had quite a unique treatment journey. What have you found most challenging so far? And, conversely, have you found any unexpected "blessings" in being thrown on this cancer journey?
The most challenging thing so far has been finding out what drives my cancer progression. We have been running after the cancer one treatment after another without any respite. It’s disappointing to see that, after so many different treatments, my medical team has not yet found a way to put ‘the beast’ under control. I have had 3 tissue biopsies and 2 liquid biopsies so far, all confirmed it’s NSCLC, ALK-positive, but none has detected any other significant targetable mutation, and it’s not sensitive to any ALK TKIs. Despite having a high PD-L1 (95% in the January 2024 biopsy), immunotherapy does not work either. So, there must be something else that is driving the cancer progression, and we have not been able to find this ‘something else’.
In terms of ‘blessings’ I found in my cancer journey, I got many:
1. First of all, I am so lucky to be in the French social security system, in which the state takes care of my treatment costs, and I have access to the best medication without having to worry about the cost and related paperwork. This is a great help for us cancer patients in France.
2. Secondly, I feel very blessed that I have a home that is so close to the best European cancer hospital where I am followed by a top ALK specialist and the best medical facilities available.
3. I am also blessed that I can have access to medical care outside of France, for example, in China, Thailand or in the UK, because I have global insurance that covers those countries. This is useful as I travel a lot and I still hope to travel when my situation gets stable. My Chinese origine also helps me access traditional Chinese medicine for treatment of daily health issues.
4. I am uniquely blessed with a daughter in medical school who is able and so readily available to assist me in my fight against the disease. I am very happy to see her dedication to cancer research, as she has been admitted to a PhD program at Cambridge University this autumn.
5. I am so blessed with a companion who is the best cook, so capable in nutritional matters, taking care of me the whole time and helping me in managing the side effects so effectively.
6. Last but not least, I was informed by my daughter of the existence of ALK Positive FB Support Group, and I joined this group as well as the French FB group and found these patients’ support groups extremely valuable.
5. I understand you keep well on top of all the latest developments in ALK cancer research. What do you consider most promising for the future of ALK, and what do you hope to see for yourself and other ALK cancer patients in the near and in the longer-term future?
I have been reading papers like many of us do. In terms of latest developments in ALK research, I think the joint paper published in early 2023 by the world’s top 3 female ALK specialists, Jaime Schneider, Jessica Lin, and Alice Shaw, titled “ALK-positive lung cancer: a moving target”, summarises them well. In terms of new drug developments, we have a number of clinical trials, the most prominent of which is NVL-655, and I am very happy to see it moving into phase II now. In addition, Alice Shaw’s talk at the 2023 ALK Summit mentioned three most promising areas: Anti-body Drug Conjugates (ADC), Radioligand therapy (RLT), and Immune Cell Engager (ICE). Plus, I believe the ALK vaccine is also a very promising area.
While we are all eager to see faster progress in cancer research and drug development, we have to face the reality that research leading to a new drug takes a long time and requires a lot of resources. As a patient with a life-threatening disease, I am more interested in short-term yields and immediate measures that could be deployed to beat ‘the beast’, to prolong my progression-free survival, instead of waiting for 5 or 10 years for the new drugs to be available.
So, what do I hope to see for myself and other ALK cancer patients in the near and in the longer-term future? Well, here is my wish list:
1. I hope to see more clinical trials leading to more new approved drugs for us.
2. I hope to see the availability of adjuvant drugs/solutions that we can take together with an existing TKI to overcome its resistance and improve its efficacy.
3. I hope to see more clinical trials in drug combinations, for example, a TKI with a chemo drug, to see if several drugs combined can be more effective through their synergistic effects than when deployed alone.
4. I hope to see and practice ways through which we can co-exist with cancer long-term. This would require a different approach to the cancer treatment than the total elimination of cancer cells. If I can co-exist peacefully with the cancer, why shall we kill it at all costs?
5. I also hope to see a more personalised holistic approach to treating our disease with a package of drugs and measures tailored to my personal conditions. This package would include the ongoing cancer treatment, be it TKI, chemo, surgery, or radiation, but also instructions about what I should eat and drink every day to reinforce treatment efficacy. It would also include the supplements (such as vitamins, curcumin, ginseng, green tea extract, etc.) I should take, the physical exercises I should do every day, etc.
6. I also hope to see more active patient participation. I believe that we patients should not passively leave our health entirely to the medical team. The medical team’s task is to kill the cancer cells, but our mission is broader: healing and survival. We need to fully cooperate with the medical team to make our body and spirit strong enough to support the medical treatments, to heal from its side effects, and to achieve long-term survival with high quality of life. There are many things we can do in this respect.
7. Patient participation starts with patient awareness. I hope to see every newly diagnosed cancer patient given a patient cancer guidebook. It would talk about what this cancer is, what are its possible causes, what are the available drug/treatment options and their possible side effects, what are the available social resources, including patient support FB groups that can help, etc. It’s very important for a newly diagnosed patient not to be left alone and feeling helpless and desperate.
This is a long list. I believe these are good topics for reflection about our future.
6. Knowing what you know now, what would you advise a newly diagnosed patient? What do you know now that you wish you knew back when you were first diagnosed?
To a newly diagnosed patient, I would say three things:
1. Welcome! You are not alone. Stop asking why you got this; anyone who has lungs could get it. Please accept it as a new challenge in life.
2. Congratulations! You are lucky to be ALK-positive, as it has so many drugs available now and many in the pipeline. You are also lucky to have patient support groups where patients can help each other.
3. Be serious! This disease is not an easy one. It’s hard to get rid of it with one single treatment or one single drug. You need to proactively manage it as if you manage a project at your work; use all the resources at your disposal, understand the disease, trace its evolution, study the treatment options at every critical moment, actively discuss and participate in the decision-making, keep all your medical records, don’t rely wholly on your doctors. Your doctor has many patients, but you only have one life.
To answer your second question, what do I wish I knew back when I was first diagnosed? Well, I wish, when I was first diagnosed, I could have had a patient guidebook that showed me what this disease was about, what kind of treatments were available, possible side effects, etc. This would have better prepared me for my journey, and I might have possibly avoided some mistakes like the ulcer in my esophagus.
Thank you for this interview. Through it, I realised that I missed Avastin 4 times in my first line of chemo. I will discuss this with my oncologist at the next consultation, whether this was the cause of failure in my first chemo line, and try to remediate it.
EDITORS NOTE: After this interview was completed, Xavier found out that his rechallenge treatment with Lorlatinib is working according to his latest scans. We wish him a long, successful run on the treatment!
Interview by: Christina Weber