Metastatic NSCL Cancer Advances
Nowadays, molecular profile of cancers guide the selection of treatments. For the subset of patients with Non Small Cell Lung (NSCL) cancer that are positive for the ALK mutation, a new ALK inhibitor called Alectinib was tested head-to-head with the standard of care Crizotinib. The results were in favor of Alectinib with a response rate of 85.8% versus 70% for Crizotinib. The adverse events profile was also in favor of Alectinib with much fewer grade three side effects, and the disease-free survivor rate was 20 months for Alectinib double that of Crizotinib. Alectinib had also improved response in brain metastasis.
Another subset of NSCL cancer patient presents with the EGFR mutation and are treated with TK1 inhibitors. When a patient with the EGFR mutation develops resistance to first line TK1 Inhibitors the tumor tissue needs to be tested for the acquired resistance mutation T790M, which can occur up to 60% of the time (liquid biopsy can be used instead of tumor tissue). The patients who develop the T790M mutation respond to Osimertini B. A third generation TK1, Osirmertini B is also an oral medication, the most common side effects are diarrhea, nail and skin changes similar to other TK1's. The response rate was 60% and the duration of response 12.4 months.
Another class of drugs proven to be very effective in NSCL cancer are the PD1-PDL1 inhibitors (proteins present on immune cells and some cancer cells). This class of drugs function as immunomodulators that stimulate the immune system to fight cancer cells. The PD1/PDL1 inhibitors currently FDA approved are Nivolumab and Pembrolizumab, these drugs have improved survival response rate in NSCL cancer compared to chemotherapy. The most common side effects were pain, decreased appetite, fatigue, and a small number of patients had immune mediated side effects (colitis, pneumonitis, hepatitis, renal disease). Numerous new drugs are currently being tested as single agents or in combination.