M. Catherine Pietanza, MD,
Immune checkpoint inhibitors have demonstrated encouraging results for patients with small cell lung cancer (SCLC) and mesothelioma, two aggressive thoracic malignancies with few options, according to a presentation by M. Catherine Pietanza, MD, at the 10th Annual New York Lung Cancer Symposium.
“The antibodies to CTLA-4, PD-1, and PD-L1 can be safely given to these patients. Responses are seen and are durable. There is a benefit in both platinum-sensitive and platinum-refractory SCLC,” said Pietanza, a medical oncologist at Memorial Sloan Kettering Cancer Center.
Chemotherapy has traditionally been the treatment of choice for most patients with SCLC and mesothelioma beyond the frontline setting. However, outcomes are poor with these therapies, specifically for SCLC, where the median survival following second-line therapy ranges from 6 to 9 months.
“Pace of development of drugs for these malignancies has lagged behind NSCLC,” said Pietanza. “Both malignancies are associated with immunogenic effects. While PD-L1 expression is minimal to nonexistent in SCLC, it is quite high in mesothelioma.”
For those with SCLC, two studies have reported their findings, with several trials ongoing. In the phase I/II CheckMate-032 trial,1
patients with pretreated SCLC received the single-agent PD-1 inhibitor nivolumab (Opdivo) or the combination of nivolumab and the CTLA-4 inhibitor ipilimumab (Yervoy).
In the trial, 80 patients received nivolumab at 3 mg/kg every 2 weeks. For the combination arm, 47 patients received nivolumab at 1 mg/kg and ipilimumab at 3 mg/kg every 3 weeks. Treatment in both arms was continued for 4 cycles followed by nivolumab alone at 3 mg/kg every 2 weeks. In the single-agent group, a majority of patients had received 2 to 3 prior therapies (60%) and 55% were sensitive to frontline platinum-based therapy. In the combination group, most patients had received 1 prior therapy (55%) and 45% were sensitive to platinum treatment.
In evaluable patients, nivolumab monotherapy demonstrated an objective response rate (ORR) of 12.7% and a stable disease (SD) rate of 16.4%. The median duration of response (DOR) had not yet been reached (range, 19.4-61.6+ weeks).
In the combination arm, the ORR was 31.1%, with a 2.2% complete response rate. The SD rate for the combination was 22.2%. The median DOR was 30.4 weeks (range, 5.7-41.8+ weeks).
Median progression-free survival (PFS) with single-agent nivolumab was 1.38 months (95% CI, 1.31-1.54). In the combination arm, median PFS was 3.35 months (1.41-6.87). The 9-month PFS rates were 10.2% and 30.4% for the single-agent and combination, respectively.
Median overall survival (OS) with nivolumab alone was 3.55 months (95% CI, 2.66-7.46) and was 7.75 months with the combination (95% CI, 3.65-NR). The 1-year OS rates were 27.1% and 47.5%, for the monotherapy and combination arms, respectively.
The treatment-related adverse events (AEs) associated with treatment were generally mild and consistent with previous experiences. All grade AEs occurred in 41.3% of patients treated with monotherapy and in 83% of those who received the combination. Grade 3/4 AEs were seen in 11.3% of those treated with nivolumab alone and in 31.9% of individuals who received the combination.
“Obviously, very impressive is the progression-free survival being 30% with the combo and about 10% at 9 months for nivolumab alone, this is quite impressive,” Pietanza said. “I don't know if we would see these results with topotecan. Some of these patients have had more than two lines of therapy.”
In the phase Ib KEYNOTE-028 trial,2
24 patients received the PD-1 inhibitor pembrolizumab (Keytruda) at 10 mg/kg every 2 weeks. All patients had received prior chemotherapy, specifically platinum/etoposide (100%), irinotecan or topotecan (46%), and/or a taxane (29%). All patients were PD-L1-positive.
With pembrolizumab the ORR was 29.2% (95% CI, 12.6-51.1), which consisted entirely of partial responses, The SD rate was 4.2% and the DOR was 29 weeks (range, 0.1-29.1 weeks). Median PFS was 1.8 months, with a 6-month PFS rate of 32.5%.
Overall, 62.5% of patients experienced a treatment-related AE of any grade with pembrolizumab. Grade 3/5 AEs occurred in 8.3% of patients, including 1 grade 5 incidence of colitis.
“There are numerous ongoing studies in small cell lung cancer utilizing these agents that are open or are about to be open at multiple institutions,” Pietanza noted. “I suggest we all look for them and enroll our patients on them—it is the only way that we are going to make very strong conclusions about these agents.”