The CDC lists lung cancer as the third most common type of cancer in the United States with the highest death rate. Estimates are given of 2.2 million patients worldwide with 1.8 million deaths annually.
In this regard, the FDA recently approved durvalumab and tremelimumab plus platinum-based chemotherapy (PBC) to treat metastatic non-small cell lung cancer (NSCL) without epidermal growth factor receptor (EGFR) or ALK.
An article in the Pharmacy Times explains that although drugs that are platinum-based treat various cancer types, they come with a series of side effects. These drugs treat ovarian, testicular, breast, and lung cancers.
About the Study
Enrolled patients randomly received:
· durvalumab plus tremelimumab and PBC;
· durvalumab plus PBC; or
· PBC alone.
The FDA approval was given on the basis of data taken from the phase 3 POSEIDON trial (NCT03164616) to investigate whether the gene for EGFR became mutated causing more rapid growth of cancer. The safety and efficacy of the combination therapy plus standard of care were also investigated.
An efficacy analysis compared 675 patients about 50% of whom enrolled in the durvalumab combination and PBC arm. The other half of the study received treatment with only the PBC.
Patients’ age ranged from twenty-seven to eighty-seven with a median age of sixty-three. Seventy-nine percent of patients reported having been either current or former smokers. Treatment was halted upon disease progression or if the patient experiences intolerable toxicity.
NSCL continues to remain a challenge to treat, as many tumors are unresponsive to not only standard treatment but also checkpoint inhibitors. The inhibitors are harmful because they prevent the immune system from killing cancer cells.
Trial Results
Patients receiving durvalumab/tremelimumab plus platinum-based chemotherapy compared against chemotherapy alone showed a twenty-eight percent decrease in risk of disease progression and/or death.
About Adverse Events
Twenty percent of patients reported fatigue, decreased appetite, diarrhea, rash, musculoskeletal pain, nausea, and diarrhea. Ten percent of patients experienced grade three or four laboratory abnormalities such as anemia, neutropenia, leukopenia, and thrombocytopenia among other adverse events.
Forty-four percent of patients who received the combination therapy experienced severe toxicities such as pneumonia, diarrhea, anemia, thrombocytopenia, febrile neutropenia, and pyrexia (fever).
Fatal reactions occurred in approximately four of the patients. These included one patient with nephritis, hepatitis, pancreatitis, and myocarditis. Two patients were diagnosed with sepsis. The following adverse reactions were also reported:
- acute kidney injury
- febrile neutropenia
- chronic obstructive pulmonary disorder
- dyspnea (labored breathing)
- sudden death
- and ischemic stroke
The lead investigator in the POSEIDON trial, Dr. Melissa Johnson stated in a recent press release that the immunotherapy combination plus chemotherapy made its debut as a reasonably well-tolerated immunotherapy option for NSCL.
