Study Finds Significant Response of Nivolumab-Refractory Lung Cancer to Salvage Chemotherapy

Physicians should be cautious when treating patients with lung cancer after progression on nivolumab because nivolumab-refractory lung cancer could have a significant response to salvage chemotherapy, according to a new study.

Although salvage chemotherapy after nivolumab therapy has demonstrated potential efficacy, there is minimal information on the clinical and immunologic features in lung cancer patients where the treatment is unsuccessful.

In a new study, published in Thoracic Cancer, the researchers hypothesized that chemotherapy improved the balance between immunostimulator and immunosuppressive cells to synergize with the immunostimulatory effects of the previous nivolumab treatment. In order to test this, the researchers conducted 2 case reports with 2 nivolumab refractory lung-cancer patients.

The first patient was a 66-year-old female, current smoker, who was diagnosed with stage IV undifferentiated non-small cell lung cancer (NSCLC) with bone metastasis. Her treatment was not successful and, following an additional 6 cycles of nivolumab, disease progression still occurred. However, when the nivolumab treatment regimen changed to the oral chemotherapy S-1 at a dose of 60 mg twice daily for 28 days, the tumor regressed and the patient remained progression-free for 5 months.

“Although the definition and exact mechanisms of pseudoprogression following nivolumab therapy remain undetermined, we considered this possibility in our cases. In Case 1, the tumor enlarged and respiratory symptom worsened after the 18-week observation period during nivolumab therapy,” the authors noted. “On review of previous clinical trials for NSCLC, symptomatic pseudoprogression was uncommon at nine weeks after the initiation of nivolumab.”

The second case report was a 75-year-old man who was a former smoker and diagnosed with stage IIIA lung adenocarcinoma with pulmonary metastases. The patient’s treatment, including chemotherapy were not originally successful and after 6 cycles of nivolumab, disease progression was evident. When the patient’s treatment changed to carboplatin/albumin-bound paclitaxel, his tumor rapidly regressed.

“In conclusion, physicians should be cautious when treating patients after progression on nivolumab because nivolumab-refractory lung cancer could show a remarkable response to salvage chemotherapy,” the study concluded.

The study calls for further research with a larger cohort to determine the extent of benefits of salvage chemotherapy and how the responders are selected.