Suresh S. Ramalingam, MD
The treatment of patients with small cell lung cancer (SCLC) has changed very little in the last few decades. However, the introduction of checkpoint inhibitors may change the prognosis for a number of patients with this disease, said Suresh S. Ramalingam, MD.
In April 2018, the FDA granted a priority review to a supplemental biologics license application for nivolumab (Opdivo) for the treatment of patients with SCLC with disease progression following 2 or more lines of therapy. Findings from the phase I/II CheckMate-032 trial showed a median overall survival (OS) of 4.4 months and a 1-year OS rate of 33% with single-agent nivolumab in patients with progressive SCLC following ≥1 prior line of therapy.1,2
Additionally, an exploratory analysis from this trial investigated the combination of nivolumab and ipilimumab (Yervoy) in patients with recurrent SCLC with a high tumor mutational burden (TMB). In this high-TMB subgroup, the combination demonstrated an objective response rate (ORR) of 46%. Additionally, nivolumab/ipilimumab had a superior ORR versus nivolumab monotherapy (21%) in this population, which Ramalingam said supports the idea that combinations may be more beneficial than monotherapy in SCLC.3
Pembrolizumab (Keytruda) has also demonstrated encouraging response rates in patients with SCLC. Findings from the phase Ib KEYNOTE-028 trial showed that pembrolizumab induced an ORR of 33% in patients with extensive-stage SCLC.4
Although there have been early signals with other agents, such as PARP inhibitors and lurbinectedin, immunotherapy remains the most promising option that is emerging for this disease, Ramalingam said. More data on novel agents will be released at the 2018 ASCO Annual Meeting, such as the full results with rovalpituzumab tesirine (Rova-T), which thus far has demonstrated underwhelming preliminary results in the third-line setting of relapsed/refractory SCLC treatment.
In an interview with OncLive
, Ramalingam, deputy director of Winship Cancer Institute of Emory University, shed light on the recent data with these agents in SCLC.
OncLive: What is the prognosis of patients with newly diagnosed SCLC?
We divide SCLC into 2 broad subgroups. There is what we call limited-stage SCLC, which is an earlier stage of lung cancer, and then there is extensive-stage SCLC, which is the typical metastatic SCLC. The prognosis is different for these 2 groups. If someone has limited-stage SCLC, we see a 5-year survival rate of approximately 25%. There is a subset of those patients whom we can cure with chemotherapy and radiation. We cannot cure patients with extensive-stage disease. Presently, the median survival is around 10 months. Their prognosis is considerably worse than those with limited stage SCLC.
The FDA recently granted a priority review to single-agent nivolumab for the treatment of patients with SCLC. Could you share some insight on the efficacy of this agent in this disease?
PD-1/PD-L1 inhibition seems to be a rational strategy in SCLC. These tumors have a high TMB, which can predict who might benefit from agents like nivolumab and pembrolizumab. There will be some phase II studies done with nivolumab and pembrolizumab. [These agents] have shown response rates of 10% to 15%. These are used in patients who have already had standard chemotherapy in the frontline setting, and then go on to get immunotherapy in the second-line setting. The median progression-free survival is relatively modest with the immune checkpoint inhibitors. At first look, one could say that there is some promise here, but we need to better understand who responds to these agents and how we can personalize therapy based on biomarkers.
There was another clinical trial in which patients either received nivolumab alone, or they got nivolumab with ipilimumab. In this experience, the combination seemed to do better than nivolumab alone. The NCCN has now included the combination of nivolumab and ipilimumab in their guidelines for second-line SCLC treatment.