After thoroughly studying the recent progression of chemotherapy and immunotherapy, the Australian researchers have called the combination of these two (immunochemotherapy) the "next frontier" to get better results in the treatment of mesothelioma cancer.
This study is published in the Expert Opinions in Biological Therapy journal on 2nd May 2019.
A team of Australian researchers at the National Centre for Asbestos Related Diseases, University of Western Australia, reviewed previously published research studies between the years 2016 and 2018 to find out the status of immunotherapeutic treatments and chemotherapy treatment on the removal of the mesothelioma tumor. Thus to get a clear picture of how to use these treatments in future clinical trials.
The researchers have shared their comprehensive reviews on the use of a combination of chemotherapy and immunotherapy as,
"Combinations of checkpoint blockade with chemotherapy are the next frontier in these clinical trials in mesothelioma, with promising initial reports and ongoing studies."
Chemotherapy is the Current First Line of Defense Against Mesothelioma
After the diagnosis of mesothelioma, surgeons use the chemotherapeutic approach as the first line of treatment, instead of immunotherapy. Chemotherapy is, by far, a highly recommended option for treating mesothelioma.
For the past several years doctors are administering, a chemotherapy drug pemetrexed (under the brand name Alimta) to the mesothelioma patients along with cisplatin (a platinum-based drug). But the survival rate of patients after this chemotherapy is very minimal, on average about 4 to 5 months.
In an attempt to increase the survival time of pleural mesothelioma patients after chemotherapy, Carboplatin was used instead of cisplatin, but the efficiency of this combination was also similar to the previous one.
Recently, in the year 2016, clinical trials are done with the combination of cisplatin and pemetrexed with the addition of bevacizumab on the malignant pleural mesothelioma patients.
The results showed significant improvement in the overall survival rate of the patients, but with some toxic effects. However, this trio has not yet been approved by the FDA for the treatment of mesothelioma; hence, it is unavailable.
However, the Australian researchers have revealed that immunotherapy drugs can enhance the immune system, and help chemical drugs to work efficiently. This combination can extend the survival rate of mesothelioma cancer patients.
Combining Immunotherapy with Radiotherapy
The Australian researchers have also reviewed the published research regarding the use of radiotherapy along with immunotherapy in an attempt to achieve a better survival rate for cancer patients. But there is more research and clinical trials needed to evaluate this combination and response of the immune system after the application of radiotherapy.
As per the results deduced by the research published in the Oncotarget Journal in 2015, titled as "Targeting the inhibitory receptor CTLA-4 on T cells increased abscopal effects in murine mesothelioma model", the researchers wrote that,
.....reduction in tumor bulk distal to the radiotherapy treated area – appears to occur with higher frequency in patients with other cancers treated with checkpoint blockade and radiotherapy, it has not been reported in human mesothelioma.
Focusing on the Immunotherapy Drugs
Immunity checkpoints regulate the whole immune system by differentiating the cancer cells from healthy cells. Thus to ensure that the immune system does not target the healthy cells in spite of cancer cells.
Cancer cells tend to hide under these blankets of the human immune system, which is the main reason for the delay in finding out the best treatment against the metastatic cancer cells, The same goes with the malignant mesothelioma cancer cells.
The cancer immunotherapy therapy targets the hiding checkpoints used by cancer cells for their protection. For this, these checkpoints are found to restore the functioning of the immune system.
Currently, PD-L1 and CTLA-4 immune checkpoints are approved to be blocked by checkpoints inhibitors.
Several studies in the recent past have shown that blocking these checkpoints can put the immune system back to the "on" mode or functioning stage in mesothelioma cancer. The checkpoint inhibitors used for this purpose are called immunotherapy drugs.
Use of Immunotherapy drugs for the blockage of these immune checkpoints is currently under research, and researchers study new inspections for the therapeutic effect of immunotherapy.
Combination of Chemotherapy with Immunotherapy
The researchers studied all the previously published studies on the blockers of both CTLA-4 and PD-L1, and they concluded that the treatment of mesothelioma cancer blockage of only CTLA-4 checkpoint through immunotherapy is not enough.
And when it comes to PD-L1 checkpoint inhibition, there are pretty good chances for better treatment of mesothelioma cancer. The researchers have evaluated that in the second treatment, this immunotherapy approach helps in 20-29% of the cases. And focus on the fact that more clinical trials are needed to compare the effects of PD-L1 checkpoint blocking immunotherapy with chemotherapy.
The wrote that,
Single-agent anti-CTLA-4 blockade has no survival benefit over placebo in pre-treated mesothelioma and should not be used. However, clinical trials using single agent PD-1 blockade in the second and subsequent line setting have demonstrated partial response rates of between 20% and 29%.....
The researchers have also deduced that, though in single blocking of CTLA-4 did not show promising outcomes but combining the blockage of both PD-L1 and CTLA-4 can increase the survival rate for mesothelioma patients.
As the reviewers wrote that,
"Current clinical trials are studying combinations of checkpoint inhibitors, with two single arms and one randomized phase II study to date suggesting a small incremental increase in response rates and possibly progression-free survival from adding CTLA4 blockade to PD-1 inhibition. Again, the use of such combinations remains experimental and should be done within the structure of a clinical trial."
The researchers have pinpointed the fact that though there are pretty good chances of getting positive results by the use of immunotherapy, still,
"At the moment, such combinations are best used within an appropriate clinical trial."
Australian experts have concluded in this review by saying that in the coming future, a combination of chemotherapy and immunotherapy will be the "next frontier" for the mesothelioma cancer treatment.