I will try to play the devil advocate and give a balanced opinion here in regards to second-line immunotherapy treatment for lung cancer.
In my first part, I put forward what pharmaceutical representatives often present to oncologists; highlighting positive numbers, glossing over large percentage reduction in risk of death and not mentioning ‘hidden’ information.
The ‘hidden’ information is actually in the clinical papers itself, if only one spend enough time to read the whole clinical paper and not just the summary.
In this second part, I’ll try to be more critical with some of the results (above table).
Reduction in Risk of Death
Immunotherapy treatment statistically improve median overall survival (OS) significantly in second line treatment of advanced/ metastatic lung cancer; reducing risk of death by about 30-40%. (excerpt from Part 1)
Sound great? The devil is in the details.
On a more sober note, just look at how many months of survival improvement, in absolute number.
- For nivolumab, it was around 3 months (2.7 – 3.2 months)
- For pembrolizumab, it was just 1.9 – 4.2 months
- For atezolizumab, it was additional 4.2 months
However, it would be insensitive of me to brush off additional 3months – 4 months of survival as insignificant.
Someone could be able to witness their love one graduate, married, give birth and hold a baby and even travel around the world in these few additional months.
Next, what does it mean by hazard ratio (HR) in survival analysis of 0.71.
- Statistically, it is normally interpreted as 29% (1.0 – 0.71 = 0.29) reduction in risk of death.
However, did the treatment actually contribute to ‘reduction in risk of death’?
No, unfortunately, all patients will eventually succumb to the metastatic disease in the end. So, this ‘reduction in risk of death’ is not only confusing but also misleading.
Progression Free Survival (PFS)
An effective immunotherapy treatment for one type of cancer doesn’t mean that it will be effective for another types of cancer.
In this case, even usage of immunotherapy in first-line or second-line lung cancer treatment differs greatly in results.
- The median progression free survival (PFS) for second-line immunotherapy treatment in lung cancer (see above table) ranges from a disappointing 2.3 months – 3.9 months only.
- Median PFS meaning how many months on treatment before the cancer cells develop resistance and progresses (yes, that means that immunotherapy only able to control lung cancer for just 2 months – 4 months only, disappointing, right?).
- PFS could be a little bit longer if taking into account new way to assess response because immunotherapy act in a different/ slower manner compared to chemotherapy.
- The PFS would not differ much from immunotherapy anyway (2.8 months – 4.2 months) if we use docetaxel chemotherapy, which is very much cheaper and fairly tolerable.
However, pharmaceuticals will emphasise on the statistically significant survival improvement (again, please read the earlier portion above, look at the absolute number of month gained instead of percentage).
Why is survival longer even when patient progresses earlier with immunotherapy?
- It is likely due to patient’s fitness and post-progression treatments (3rd, 4th or subsequent lines of treatments).
- Any incremental benefits above can easily be negated if patient is not eating (losing weight) and exercise enough (losing muscle mass).
The price of immunotherapy treatment is exorbitant, not just expensive (I’ll show some numbers below).
- I do hope that someday, payment of any immunotherapy treatments to pharmaceutical companies will be based on the results that patients able to achieve. An audit of its effectiveness and also the side effects should be conducted regularly.
- Insurance is important to protect against financial catastrophe when someone is unwell, unable to work and yet have to fork out a lot of money for treatment. Please get an insurance coverage if you can afford it.
- Nationwide insurance scheme should be expanded to cover more people and more diseases in order to offer more benefits. However, I doubt this will happen when initial rollout of National B40 Protection Scheme/ mySalam had been criticised left, right and centre. Everything has to be politicised in Malaysia, even when the government main concern is for Malaysians well being.
The cost of docetaxel medication alone for single cycles ranges from 1000-1500 per cycle (depending on dose).
The cost of immunotherapy treatment for atezolizumab alone is RM12500-15000 per cycle (I heard nearing 20k per cycle in KL). There is patient assistance programme; buy 2 cycles, free 1 cycle, average about RM8000-13000 per cycle.
Better still, in second line treatment for lung cancer, pharmaceutical giants even said no PD-L1 testing is needed before starting immunotherapy treatment.
- High PD-L1 expression will indicate better response and better results.
- So, it means those patient who might have negative PD-L1 test result (if tested), which respond poorly to immunotherapy will also be started on these expensive and unnecessary treatment.
For one patient on immunotherapy, 8-10 other patients can benefit from docetaxel chemotherapy with fairly similar results in second-line lung cancer treatment
And if one pay from own pocket, with savings of RM8000-10000 with chemotherapy and obtaining similar PFS results, the extra money can be use for more nutritional foods, travelling and other more uplifting activities.
So, Immunotherapy is Not Effective?
Of course not.
It’s all about proper patient and treatment selection and individualising treatment plan.
If a patient unable to tolerate or allergic to chemotherapy, I’ll know that immunotherapy is just as effective to replace chemotherapy.
Both chemotherapy and immunotherapy have its own sets of side effects and it’s my job to minimise, anticipate and deal with it.
It’s vital to have expanded armamentarium of treatments (chemotherapy, immunotherapy, biologic therapy, targeted therapy) against cancer.
Stage 4 cancer patients live longer nowadays because of the availability of 2nd-, 3th-, 4th-, 5th-, 6th-lines and many more lines of treatments.
Patient who is fit (eat!, exercise!) will be able to have more lines of treatments, which will translate to longer survival. Treatment toxicity is also lesser and milder if a patient is fit.
Immunotherapy use in second-line lung cancer treatment might be equally effective as first-line if PD-L1 expression is high enough.
- Use it wisely in high PD-L1 expression.
- Using immunotherapy when PD-L1 is negative or low is useless.
Immunotherapy is very effective in first-line treatment of lung cancer (those with high PD-L1 expression) and in several other cancers (melanoma, haematological cancers, etc).
Also, combination treatment (immunotherapy + chemotherapy) is also effective and logical steps as tumor is heterogenous (those cancer cells who are resistance to immunotherapy can be dealt with chemotherapy and vice versa).
I will try to write more about immunotherapy benefits in first-line treatment of lung cancer in future.