Tyrosine kinase inhibitor (TKI) has been widely used as a cancer therapy for patients who have EGFR mutations. However, patients who have EGFR mutations only benefit from EGFR-TKI therapy for less than 1 year, because after that there will be resistance.
Patients who experience progressive or deteriorating condition after TKI administration as first-line therapy, according to the 2017 NCCN, an exam must be done to identify any T790M mutations. If a positive T790M mutation result is obtained then the treatment choice is a third generation TKI (Osimertinib). Many recent studies have proven the effectiveness and response of Osimertinib therapy which is quite significant against lung cancer with the EGFR T790M mutation.
The author reported the management of a pulmonary adenocarcinoma patient with a positive EGFR mutation with a first-line EGFR TKI therapy deteriorated condition and T790M mutations at Dr. Soetomo Hospital.
First-line therapy is given to patients who have never received treatment before. All patients who have been diagnosed with adenocarcinoma can be given first-line platinum-based chemotherapy right from the start or after the results of the EGFR mutation examination are known. If the EGFR mutation is known from the start, TKI EGFR therapy should immediately be first-line therapy option. On the other hand, if the EGFR mutation exam is negative, then platinum based chemotherapy can be given. Furthermore, after the administration of EGFR TKI therapy, the patients were observed. If the condition worsens due to a T790M mutation, then the next treatment option should be the second-line EGFR TKI (Osimertinib) (Sequist et al 2011, Thomas et al 2004, WHO 2004).
Adenocarcinoma patients with EGFR mutations will initially respond strongly to TKI EGFR therapy, but will subsequently experience secondary resistance to these drugs on average for a period of 9-14 months (Mok et al 2009, Sequist et al 2011).
Method and Results
A patient named Mr. J, 54 years working as a builder with a history of smoking 1 pack per day for 32 years, came with complaints of coughing up blood. Other complaints were cough with thick white phlegm, weak body, decreased appetite, and decreased body weight, fever and intermittent shortness of breath.
Anatomic pathology examination results showed pulmonary adenocarcinoma with a positive mutation EGFR examination on exon 19. Patients were given first-generation Tef Gefitinib 125 mg therapy daily orally for 7 months. Initially the patient experienced a fairly good response to treatment with the results of a thoracic CT scan recist criteria partial response, but entering the seventh month, the first-line TKI EGFR treatment did not work anymore until the patient entered hospitalized.
There was a clinical deterioration in the form of shortness of breath and cough, fever, nausea, vomiting, coughing up blood, decreased appetite, decreased body weight. In addition, there was also leg edema as a sign of VCSS (a set of symptoms due to vein dilation) and led to onset tumor. There were also signs of massive pleural effusion that fills the entire right lung field. It was assessed from the radiological thoracic CT scan that the patient experienced an increase in tumor mass> 25% with recist progressive disease criteria.
After CT-DNA examination in patients, mutations were obtained at T790M. Patients should be given a second-line TKI (Osimertinib), but because the drug is not yet available in Indonesia, patients are temporarily given Docetaxel second-line chemotherapy in 4 series.
The patient then followed the early access Osimertinib program with a significant therapeutic response in the form of clinical and radiological improvement. Patients who were initially tight, coughed, weak and have difficulty moving, within 5 days after administration of Osimertinib, are getting better. Haematological markers and signs of VCSS appear to be improving. In the evaluation using chest X-ray, the tumor and effusion were significantly reduced. Until finally the patient can continue with outpatient therapy. During outpatient care, patients do not complain any shortness of breath and coughing, appetite improves and body weight is reported to improve as well.
Author: Dr. Laksmi Wulandari, dr., Sp.P (K), FCCP
Details of the research available at:
Sahrun and Laksmi Wulandari (2019). Management of Progressive Lung Cancer Patients After First-Line EGFR Tyrosine Kinase Inhibitor Therapy. Fol Med Indones, 55(3): 239-245.