Combining Interleukin-2 With Gefitinib Increased Response Rates in Patients With Advanced Non–Small Cell Lung Cancer
Adding interleukin-2 to gefitinib (Iressa) therapy resulted in threefold higher response rates in patients with advanced non–small cell lung cancer (NSCLC), according to a study by Bersanelli et al in Cancers. The addition of interleukin-2 enhanced the efficacy of gefitinib without negatively affecting adverse events.
The concept of harnessing the immune system in patients with lung cancer has seen renewed interest with the emergence of newer therapeutic targets in immunotherapy. This focus has centered on the role of interleukin-2 in the growth, proliferation, and differentiation of T lymphocytes in patients with NSCLC. Indeed, previous studies of patients with NSCLC treated with interleukin-2 demonstrated a relatively long survival. More recent studies have targeted the role of epidermal growth factor receptor-tyrosine kinase inhibitor therapy and cytokines such as interleukin-2. One such example of this type of therapy involves the use of gefitinib.
The most recent studies have projected a case for combining gefitinib with interleukin-2, which has the potential to reverse resistance to a tyrosine kinase inhibitor in patients with NSCLC. Thus, the investigators attempted to evaluate whether the use of interleukin-2 increased the efficacy of gefitinib in patients with advanced NSCLC.
Study Details
During a 3-year period, 70 patients with advanced, progressive NSCLC who had previously received chemotherapy were evaluated. These patients, who were from the oncology unit of the Istituti Ospitalieri of Cremona, Italy, received oral gefitinib (250 mg daily) or gefitinib combined with subcutaneous interleukin-2. Response assessments based on Response Evaluation Criteria in Solid Tumors group criteria were scheduled every 10 to 12 weeks (or before, in the case of clinical suspicion of disease progression).
Eligibility criteria for participants in the study included age greater than 18 years; histologic or pathologic confirmation of NSCLC; and prior treatment with at least one chemotherapy regimen for recurrent or metastatic disease, including at least one platinum-based combination. The medium age of participants in the trial was 70 years (range = 39–84 years). Fifty-three patients (76%) received only one prior chemotherapy regimen, whereas 17 patients (24%) received at least two prior lines of treatment. The median follow-up time was 25.2 months (range = 8.3–39.4 months).
Response Rate Higher With Interleukin-2 and Gefitinib
The response rate for the group receiving interleukin-2 and gefitinib was threefold higher than that for the group receiving gefitinib alone (16% vs 5%). However, the disease control rate was similar in the two treatment groups.
As for toxicity, the safety of gefitinib did not seem to be affected by its coadministration with interleukin-2. The percentage of adverse effects such as skin rash, diarrhea, asthenia, and anorexia was similar to that found in previous trials. In addition, the toxicity profile of interleukin-2 seen in this study appeared to be easily manageable and did not significantly affect the overall tolerability of the combination therapy.
As for overall survival, it was significantly higher in patients receiving the combination therapy (20 months) than in those receiving gefitinib alone (7 months). However, the investigators suggested that these numbers may have been skewed by the imbalance in patients’ characteristics between the two treatment groups. One such factor that was not accounted for was the presence of epidermal growth factor receptor–mutated tumors.
Closing Thoughts
The results of this phase II pilot study suggest that the addition of interleukin-2 may improve the objective response rate of gefitinib monotherapy in patients with advanced NSCLC.
The investigators concluded, “Further investigations with randomized controlled trials would be needed to definitely verify the efficacy of these drugs associations for non-small cell lung cancer patients.”
Melissa Bersanelli, MD, of the Medical Oncology Unit, University Hospital of Parma, Parma, Italy, is the corresponding author of this article in Cancers.
The authors reported no potential conflicts of interest.
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