Apar Kishor Ganti, MD
Immunotherapy has risen to the forefront of thoracic oncology; however, challenges exist with comparing checkpoint inhibitors and how to best select patients for this class of agents, whether alone or in combination. This is a good problem to have, according to Apar Kishor Ganti, MD.
Over the past year, positive data have been presented from several clinical trials in lung cancer. Checkpoint inhibitors like pembrolizumab (Keytruda) and atezolizumab (Tecentriq), when combined with standard chemotherapy, have been clinically proven to improve patient response compared with chemotherapy alone.
Updated data from the KEYNOTE-189 trial, presented at the 2018 AACR Annual Meeting and published in the New England Journal of Medicine
, indicated that frontline pembrolizumab plus carboplatin/pemetrexed reduced the risk of death by more than 50% in patients with nonsquamous non–small cell lung cancer (NSCLC) without EGFR
At a median follow-up of 10.5 months, the estimated 12-month overall survival (OS) rate was 69.2% (95% CI, 64.1%-73.8%) with pembrolizumab versus 49.4% (95% CI, 42.1%-56.2%) with chemotherapy alone (HR, 0.49; 95% CI, 0.38- 0.64; P
<.001). The combination was granted an accelerated approval in this setting off of prior data in May 2017.
Moreover, in May 2018, the FDA granted a priority review designation to a supplemental biologics license application for atezolizumab in combination with bevacizumab (Avastin), carboplatin, and paclitaxel for first-line treatment of patients with nonsquamous NSCLC.
This decision was based on findings from the phase III IMpower150 trial, which showed that the addition of atezolizumab improved progression-free survival (PFS) compared with bevacizumab and chemotherapy alone. A 41% reduction in the hazard for progression or death (HR, 0.59; 95% CI, 0.50-0.70; P
<.0001) was induced by the addition of the checkpoint inhibitor.3,4
Several other advancements in the field have resulted in an “exciting time for lung cancer treatment,” said Ganti, a professor of internal medicine in the Division of Oncology/Hematology at University of Nebraska Medical Center.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on A Summer of Progress: Updates from ASCO 2018, Ganti discussed some of the most intriguing abstracts in lung cancer recently presented.
OncLive®: What are some of the major updates in lung cancer research?
: There have been a lot of exciting changes in the management of patients with lung cancer over the past year. The biggest change has been the increasing use of immunotherapy, mainly the checkpoint inhibitors such as pembrolizumab and atezolizumab. A lot of exciting data have been presented in the last several months, whether at the 2018 ASCO Annual Meeting or other [meetings]. What I spoke about was a summary of some of those abstracts.
One of the big abstracts [at the 2018 AACR Annual Meeting and the 2018 ASCO Annual Meeting] was KEYNOTE-189, which showed for the first time [in a phase III setting] that adding pembrolizumab to chemotherapy was better than pembrolizumab alone in patients with advanced nonsquamous NSCLC who did not have EGFR or ALK driver mutations. What this study did was take patients with treatment-naïve stage IV disease and randomize them to either chemotherapy or chemotherapy and pembrolizumab. The trial showed that regardless of PD-L1 expression, the addition of pembrolizumab improved OS. Another study presented at the 2018 ASCO Annual Meeting was similar, looking at a similar patient population. This time the combination used was standard chemotherapy and bevacizumab with or without atezolizumab. Again, in this trial, there seemed to be an improvement in OS with the addition of atezolizumab to the background of carboplatin/paclitaxel and bevacizumab.
In addition, a presentation at the 2018 ASCO Annual Meeting that looked at patients who had a PD-L1 expression of ≥1%. That study looked at comparing pembrolizumab alone with the combination of carboplatin/pemetrexed. This showed that if you had a PD-L1 expression of ≥1%, pembrolizumab was better than the combination. However, most of this benefit seemed to be in the patient population with a PD-L1 expression of ≥50%. When they looked at the other subset of patients, there was still a small benefit with pembrolizumab, but it did not reach statistical significance.
There was also a study [conducted in Southeast Asia] of EGFR
-mutant patients [that] looked at gefitinib (Iressa) versus dacomitinib. They found that dacomitinib was associated with a better OS than gefitinib. One thing we don’t know is how dacomitinib really fits into the treatment of EGFR
-positive disease because there have been other studies with many different agents. It’s unclear what works best at this time, but it’s good that we have options.