Immunotherapies Are Effective in Lung Cancer with Proper Planning

When determining our treatment options for patients, it is very important to identify the most appropriate targeted treatment. We can determine this by examining genetic changes or special staining characteristics in the cancer cell. Immune therapies, breakthrough drugs in many types of cancer that act by stimulating the immune system, were among the main discussion topics at the ESMO 2016 Congress. Three important studies on immunotherapy in lung cancer treatment were published.

Immunotherapy as the Initial Treatment Option in Lung Cancer: KEYNOTE-024 Study Results

The first and perhaps most important of these was the study conducted in the treatment of Non-Small Cell Lung Cancer (NSCLC) with the immunotherapy drug called Pembrolizumab (Keytruda) . The study compared chemotherapy with immunotherapy as the first treatment option immediately after cancer diagnosis in patients with fourth-stage, that is, metastatic disease. In this study called KEYNOTE-024, patients were not selected at random. The selected group of lung cancer patients had a proportion of tumor cells staining for PD-L1, a protein produced by the cancer cell that blinds the immune system, of 50% or more. Thus, the patient group in whom immunotherapy could be most effective was selected. Approximately 30% of newly diagnosed NSCLC patients were found to have staining of 50% or more for PDL-1.

In this selected patient group, the platinum-containing chemotherapy combination used as standard treatment in daily practice was compared with the immunotherapy agent Pembrolizumab. The study included patients from 16 countries, totaling 305 patients. While 28% of patients in the chemotherapy arm showed significant shrinkage in tumor size, this rate rose to 45% in the immunotherapy arm. Time until disease progression was more than 10 months with immunotherapy, whereas this benefit period remained at 6 months with chemotherapy. A significant increase in survival was found in patients receiving immunotherapy. When the two treatment arms were compared for side effects, the side effects observed with immunotherapy were significantly fewer than those in chemotherapy patients.

These results give us the impression that immunotherapy will take precedence over chemotherapy in lung cancer treatment when the right patients are selected. Although immunotherapy is not yet an approved initial treatment choice for lung cancer, these positive results suggest that it will receive approval for selected patients in the coming period. The study results were published in the October issue of the internationally respected medical journal New England Journal of Medicine (NEJM) (1).

One of the Most Important Determinants of Treatment Success: Appropriate Patient Selection

Despite the success of this treatment, a different study in initial treatment of non-small cell lung cancer tested another immunotherapy agent, Nivolumab, against chemotherapy and ended in failure. Nivolumab is an FDA-approved drug that has achieved significant successes in malignant melanoma that has spread through the body, that is, fourth-stage disease, renal cell cancer, second-line lung cancer treatment and head and neck cancer.

The failure of Nivolumab as first-line treatment in this study sparked heated discussions at ESMO. After Nivolumab proved successful in a phase l study as initial treatment for lung cancer, a phase lll study had been undertaken. When nivolumab was compared with chemotherapy in 541 patients with non-small cell lung cancer that had spread through the body and who had not received chemotherapy, time until disease progression was found to be better in those receiving chemotherapy (2).

The reason for this failure may have been the lack of careful patient selection. While the first study included patients with PD-L1 staining percentages of 50% or more, this study used 1% as the cutoff value. These two studies show us that greater selectivity is needed when choosing immunotherapy as first-line treatment for non-small cell lung cancer.

The Role of Immunotherapies in Second-Line Treatment Is Becoming Stronger

In the third study presented in this field, in second-line treatment for non-small cell lung cancer, that is, patients who had received one line of chemotherapy and whose disease had progressed, the immune system stimulant Atezolizumab (Tecentriq) , was compared with Docetaxel, the chemotherapy drug accepted as standard treatment. Immunotherapy was found superior to chemotherapy in the study (3). Patient selection was observed not to be very important for this superiority. The increase in survival observed in patients receiving immunotherapy was independent of both the PD-L1 staining rate in cancer cells and the subtype of non-small cell lung cancer. The superiority achieved with immunotherapy in this study suggests that it may stem from increased sensitivity to immunotherapies after the cancer cell’s exposure to chemotherapy, or from the biological structure of Atezolizumab itself.

These studies published at the ESMO congress demonstrated the importance of correct timing as well as appropriate patient selection in using immunotherapy for non-small cell lung cancer treatment. Despite all these data, many unknowns remain in this field.

Immunotherapies are very expensive treatments and are not yet covered by reimbursement in our country. For patients with Non-Small Cell Lung Cancer receiving second-line treatment, that is, individuals whose disease progresses after chemotherapy, use of immunotherapy drugs is approved upon application to the Ministry of Health Off-Label Drug Board, provided the patient pays the cost. We recommend that individuals with private insurance or the means to pay discuss with their oncologists whether these drugs are appropriate for them.