Janakiraman Subramanian, MD
In recent years, several advances have been made in the lung cancer space, particularly in squamous non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), said Janakiraman Subramanian, MD, and groundbreaking data from 2 key pivotal trials—KEYNOTE-407 and IMpower133—have resulted in practice-changing outcomes for these patients.
“Just seeing the pace of progress of how we treat, how we approach patients over the last 5 years has been so exciting,” said Subramanian. “We’ve all had to keep pace with the changes, and just this year, we’ve had so many phase III trial data coming out and getting published in the New England Journal of Medicine
, not just in the immunotherapy space, but also in the targeted therapy space, which is very promising and very exciting.”
In the phase III KEYNOTE-407 trial, combining the PD-1 inhibitor pembrolizumab (Keytruda) with chemotherapy reduced the risk of death by 36% versus chemotherapy alone in patients with metastatic squamous NSCLC.1
Those who received the pembrolizumab regimen had a median overall survival (OS) of 15.9 months (95% CI, 13.2–not evaluable) compared with just 11.3 months (95% CI, 9.5-14.8) with chemotherapy alone (HR, 0.64; 95% CI, 0.49-0.85; P
= .0017). The addition of pembrolizumab also improved progression-free survival (PFS) in these patients. The median PFS was 6.4 months with the investigational regimen (95% CI, 6.2-8.3) versus 4.8 months (95% CI, 4.3-5.7) with chemotherapy alone (HR, 0.56; 95% CI, 0.45-0.70; P
These data led to the October 2018 FDA approval of first-line pembrolizumab for use in combination with carboplatin and either paclitaxel or nab-paclitaxel (Abraxane) for the treatment of patients with metastatic squamous NSCLC, a new standard of care.
In the IMpower133 trial, the addition of atezolizumab (Tecentriq) to standard upfront carboplatin and etoposide was found to significantly prolong survival in patients with extensive-stage small cell lung cancer (SCLC).2
After a median follow-up of 13.9 months, the median OS was 12.3 months (95% CI, 10.8-15.9) in those who received the atezolizumab regimen compared with 10.3 months (95% CI, 9.3-11.3) in those who received placebo (HR, 0.70; 95% CI, 0.54-0.91, P
= .0069), which equates to a 30% reduction in the risk of death.
This is the first time in 20 years that a new initial treatment option for extensive-stage SCLC has delivered a clinically meaningful survival benefit. As such, the FDA granted a priority review designation to the supplemental biologics license application (sBLA) for the agent. The FDA action date for a decision on the sBLA is March 18, 2019.
In an interview during the 2018 OncLive
® State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Subramanian, a medical oncologist and director of thoracic oncology and director of the Center for Precision Medicine at St. Luke’s Cancer Institute, discussed ongoing advances and remaining challenges in the field of lung cancer.
OncLive: Could you discuss recent trials that have led to major advances in lung cancer treatment?
: The KEYNOTE-407 study was [conducted] primarily [in patients with] squamous cell lung cancer and looked at giving chemotherapy plus pembrolizumab, which is a PD-1 inhibitor. Patients were randomized to receive carboplatin plus paclitaxel plus pembrolizumab versus carboplatin/paclitaxel alone. They also got placebo on that arm. They were looking at the co-primary endpoints with PFS and OS and patients were randomized to either arm, irrespective of their PD-L1 status.
Therefore, whether patients were PD-L1–negative or –positive, they were still able to go on the study and receive immunotherapy. What they clearly showed was that the OS was significantly better in patients on the immunotherapy arm. Similarly, the PFS was also better. Across all treatment parameters, adding immunotherapy for patients with squamous cell lung carcinoma improved their outcomes.
Adverse events were not anything unexpected from what we already knew about immunotherapy and chemotherapy combinations. Definitely, that is the next step in how we treat squamous cell lung carcinomas; until now, chemotherapy has been the primary first-line treatment, but this study has changed that. Now, that we are using chemotherapy combined with immunotherapy and that's becoming the standard of care in how we treat these patients.
[Two other important studies] were IMpower131 and IMpower133. In the SCLC study in which patients were randomized to receive carboplatin/etoposide plus atezolizumab or carboplatin/etoposide plus placebo.