The effective targeted drugs for the lung cancer treatment: 6 treatments and evidence-based findings

The effective targeted drugs for the lung cancer treatment: 6 treatments and evidence-based findings

Hasan Kobat

Written by Hasan Kobat on 17 Jan 2023

Lung cancer has been the primary cause of death due to cancer, worldwide. According to published data, more than 2 million (1) patients were diagnosed with lung cancer in 2020 and this is 11.4% of all cancer cases. It is not interesting that the number of patients who died because of lung cancer is more than other cancer types and reached to 1,796,144 (1) patients in 2020. Despite tragic statistics, improvements in drug development had resulted in the discovery of novel treatments which are effectively used for the treatment of lung cancer.

How was the treatment of lung cancer in the past?

Lung cancer treatment options were very limited in the past. Platinum-based agents such as cisplatin and carboplatin were the primary drugs that have been used for the treatment of lung cancer. Paclitaxel, docetaxel, bevacizumab and some other drugs were in use. The complete list of the medications approved by the FDA was listed by National Cancer Institute and can be found here.

According to an investigation published in the Journal of Clinical Oncology (2), the majority of the patients receiving cisplatin and carboplatin together with other old agents such as etoposide, paclitaxel, docetaxel and gemcitabine died within the first year after diagnosis of lung cancer.

Although the type of cancer drug has a significant impact on the survival of the patients, the stage at the diagnosis is also an important factor affecting survival time. Unfortunately, the majority of lung cancer cases are detected late because of their silent nature.

Innovation of new strategies and new medications in the treatment of lung cancer patients had become indispensable. Old agents were no longer effective and patients living with lung cancer was surviving less than a year.

How do the new cancer drugs fight cancer in the body?

Interestingly, after many years of using the same technique in lung cancer, the development of novel technology drugs changed cancer care. Lung cancer care has evolved with new innovations that are way different than old treatment options. Targeted therapies and immunotherapy have drastically changed the way we look at cancer treatment.

Unlike in the past, targeted therapies work another way around. The old drugs were designed to kill the cancer cells but targeted therapies work differently

Researchers revealed that there are some places on the cells, or let’s say molecules that have effects on the growth and spread of the cancer cells. Cancer researchers came up with a hypothesis that if we can block the activity of those molecular targets, we can also stop the growth and spread of cancer cells. That has been one of the most important hypothesis which led to innovations of targeted therapies in cancer care.

The innovation of immunotherapy was different than targeted treatments. Researchers hypothesised that if we can boost the body’s immune system to fight cancer cells can result in an effective strategy and observed that boosting the defense mechanism of the body, improves the human immune system’s ability to fight cancer more effectively.

That is why targeted therapies and immunotherapies used in the treatment of lung cancer are no longer called chemotherapy. They are called anti-cancer treatments because they are not directly killing cancer cells but create an environment in the human body to fight cancer.

The use of targeted treatments and immunotherapy resulted in better patient outcomes with improved survival rates. Here we listed some of the effective targeted treatments that are being used in the treatment of lung cancer. The effectiveness of immunotherapy in lung cancer will be discussed in another article.

A female doctor in visor and protective gloves examines an X ray of a patient
A female doctor in a visor and protective gloves examines an X-ray of a patient

What are the new targeted drugs that are effectively being used in the treatment of lung cancer?

Gefitinib

Gefitinib is a first-generation tyrosine-kinase inhibitor type of anti-cancer drug that is classified under targeted therapies. Gefitinib can only work if there is a receptor called epidermal growth factor receptor (EGFR) on cancer cells. EGFR plays a role in cancer cell growth. Gefitinib blocks the activity of EGFR and stops the growing rate of cancer cells.

Unlike old cancer drugs that we named chemotherapy above, gefitinib is a tablet that is taken via mouth.

There are available published studies showing the effectiveness of gefitinib in lung cancer patients.

According to a study published in the leading cancer journal Lancet Oncology (3), patients were divided into two groups. One group received gefitinib tablets and other group received cisplatin (the old agent). The average time for the patients living without symptoms of lung cancer after the end of treatment was 28.7 months in patients receiving gefitinib but this was only 18 months with the old agent, cisplatin.

Another study published in the Journal of Clinical Oncology (4) presented that the average total survival after lung cancer diagnosis of the patients receiving gefitinib is 50 months which has been a remarkable achievement. The same publication also showed that the patients who received gefitinib didn’t show any symptoms of lung cancer for more than 20 months on average.

Afatinib

The mechanism of action of afatinib is similar to gefitinib. It is also targeting EGFR and inhibits cancer cell growth. Similar to gefitinib, afatinib is also taken via mouth which means it is a tablet. There are various published studies that assessed the effectiveness of afatinib.

The results of the effectiveness of afatinib are similar to gefitinib when compared with old drugs or in other words with chemotherapy. In a group of lung cancer patients who received afatinib, the total time for survival after diagnosis of lung cancer was more than 28 months (5).

Crizotinib

Crizotinib is also a targeted therapy and targets anaplastic lymphoma kinase (ALK). Like other targeted therapies, crizotinib is also taken by mouth. Crizotinib is also one is more effective than chemotherapy.

According to a study published in The New England Journal of Medicine, the overall survival which also means the total lifespan of the patients after lung cancer diagnosis was 17.4 months (6) in patients who received crizotinib which was similar to the chemotherapy group. Progression-free survival or in other words, time for having no symptoms of lung cancer after the end of the treatment was 10.9 months (7) in patients receiving crizotinib. This was 7 months for the patients who received traditional chemotherapy.

Another significant study published in The New England Journal of Medicine (8), presented that the average time of not having any signs of lung cancer after the treatment with crizotinib was 7.7 months. This may seem quite low but when compared with the chemotherapy group within the same study, it was 3 months that shows crizotinib was more effective than chemotherapy.

Ceritinib

Ceritinib is very similar to crizotinib and it also targets ALK to block cancer cell growth. It is also taken via the mouth and is more effective than chemotherapy.
The table below summarised two studies that assessed the effectiveness of ceritinib over traditional chemotherapy. We summarised the effect of crizotinib on:

  1. Average time of having no symptoms of lung cancer after the end of ceritinib treatment which is also named “progression-free survival”.
  2. Average total survival time of the patients who received ceritinib after the diagnosis of lung cancer which is also named “overall survival”.
  3. The average proportion of the patients whose lung cancer was destroyed or got smaller or somehow showed a response to treatment with ceritinib which is also named “overall response”.
Progression-free survival Overall survival Overall response
Study 1

Ceritinib: 16.6 months

Chemotherapy: 8.1 months

Ceritinib: 29.3 months

Chemotherapy: 26.2 months

Ceritinib: 72.5%

Chemotherapy: 26.7%

Study 2

Ceritinib: 9.8 months

Chemotherapy: 1.6 months

Ceritinib: 23.9 months

Chemotherapy: 22.8 months

Ceritinib: 54.5%

Chemotherapy: 0 %

It is crystal clear that in both studies ceritinib was more effective than chemotherapy.

Alectinib

Alectinib also targets ALK to inhibit (synonym: block) cancer cell growth. Its administration is via the mouth or in medical terms “oral route”.

As cancer research is getting more developed than in the past, trials have been started to be among the novel drugs rather than comparing them with old agents only. Until here, we demonstrated the effectiveness of the novel cancer drugs over traditional chemotherapy but researchers had also started to check the effectiveness of the novel drugs over other novel drugs that have been discovered earlier.

The efficacy of alectinib was tested with crizotinib in most of the studies (crizotinib explained above). In a study published in the Lancet (9), alectinib was found to be more effective than crizotinib. The average time for having no symptoms after the treatment with alectinib was 20.3 months and that was 10.2 months in crizotinib group. This means that alectinib is two times more effective than crizotinib in terms of time for showing lung cancer signs after the end of the treatment.

The ratio of patients who developed side effects that required treatment termination was less with alectinib when compared to crizotinib. Only 9% of the patients were required to stop treatment due to side effects of alectinib but this was more than 20% for the patients receiving crizotinib.

A doctor comforting mature woman after chemotherapy in clinic
A doctor comforting a mature woman after chemotherapy in a clinic

Osimertinib

Osimertinib is also a targeted anti-cancer treatment. It is similar to its class of drugs but with a difference. Osimertinib targets T790M. It was observed that nearly 50% of the patients whose lung cancer progressed had this mutation. To date, osimertinib is the most effective drug in lung cancer which has a T790M nature. The mechanism is quite complex but osimertinib blocks cancer cell growth by having favourable effects on EGFR (explained in the beginning) T790M point mutations.


Osimertinib is more effective than gefitinib. The average time of having no signs of lung cancer after the treatment was quite higher with osimertinib and that is 18.9 months when compared to 10.2 months with gefitinib (10). The table below shows the effectiveness of osimertinib over other drugs:

  1.  Average time of having no symptoms of lung cancer after the end of ceritinib treatment which is also named “progression-free survival”.
  2. Average total survival time of the patients who received ceritinib after the diagnosis of lung cancer which is also named “overall survival”.
  3. The average proportion of the patients whose lung cancer was destroyed or got smaller or somehow showed a response to treatment with ceritinib which is also named “overall response”.
Progression-free survival Overall survival Overall response
Study 1

Osimertinib: 18.9 months

Gefitinib/erlotinib: 10.2 months

The total ratio of the patients who survived was 83% in the 18th month with osimertinib.

The ratio of alive patients in the 18th month was 71% with gefitinib/erlotinib.

Osimertinib: 80%

Gefitinib/erlotinib: 76%

Study 2

Osimertinib: 10.1 months

Chemotherapy: 4.4 months

Not applicable

Osimertinib: 71%

Chemotherapy: 31%

Note: Although this article is focused on some of the targeted therapies, there are some other targeted therapies used in the treatment of lung cancer which will be covered in another article.

Conclusion

Overall, lung cancer has been one of the biggest threats in cancer care due to its frequently observed nature and also the fact that it causes the death of patients dramatically. The significant improvements in cancer care had improved the life span of lung cancer patients and the total survival increased.

Patients should bear in mind that the treatment of lung cancer depends on various factors such as the stage of cancer, the type of the tumour and also a patient's background as well.

10 Sources

  1. Global Cancer Statistics 2020 https://pubmed.ncbi.nlm.nih.gov/33538338/
  2. Journal of Clinical Oncology https://pubmed.ncbi.nlm.nih.gov/15326195/
  3. The Lancet Oncology https://pubmed.ncbi.nlm.nih.gov/29174310/
  4. Journal of Clinical Oncology https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.9005
  5. The Lancet Oncology https://pubmed.ncbi.nlm.nih.gov/25589191/
  6. The New England Journal of Medicine https://pubmed.ncbi.nlm.nih.gov/25470694/
  7. The New England Journal of Medicine https://pubmed.ncbi.nlm.nih.gov/25470694/
  8. The New England Journal of Medicine https://pubmed.ncbi.nlm.nih.gov/23724913/
  9. Lancet https://pubmed.ncbi.nlm.nih.gov/28501140/
  10. The New England Journal of Medicine https://pubmed.ncbi.nlm.nih.gov/29151359/