Partial response more likely in advanced NSCLC patients pretreated with PD-1-PD-L1 checkpoint inhibitors

By Liz Meszaros, MDLinx
Published May 8, 2017

Key Takeaways

Pretreatment with a PD-1/PD-L1 checkpoint inhibitor makes a partial response 30% more likely in patients with advanced non-small-cell lung cancer (NSCLC) requiring salvage chemotherapy, according to results presented at the European Lung Cancer Conference held in Geneva, Switzerland.

“Our results are of utmost importance for NSCLC patients,” said lead investigator Sacha Rothschild, MD, PhD, from University Hospital Basel, Department of Medicine, Division of Oncology, Switzerland.

“Checkpoint inhibitors are currently the standard of care for NSCLC patients in the 2nd-line setting after chemotherapy and are used for a subset of patients with high PD-L1 expression as front-line therapy. So far, it is unclear how to treat patients not responding to immune checkpoint inhibitors or progressing after initial response to these agents. The activity of conventional chemotherapy in this setting has not been investigated so far. Therefore, these results are good news for patients that progress after immunotherapy and are still fit enough to receive further palliative therapy.”

In their study, Dr. Rothschild and colleagues included 82 patients with stage IV NSCLC, a cohort that included 63 patients with adenocarcinoma, 18 with squamous cell carcinoma, and 1 with large cell carcinoma.

In all, 67 patients had undergone previous treatment with a PD-1/PD-L1 inhibitor, and this included 56 patients treated with nivolumab, 7 with pembrolizumab, and 4 with atezolizumab. The remaining 15 patients who had not been treated served as controls.

All patients had been pre-treated with chemotherapy (mean: 2.37 prior regimens in cases, 1.93 in controls). Salvage chemotherapy included docetaxel (62%), pemetrexed (20%), paclitaxel (6%), and other (12%).

During the first month and every 6 weeks thereafter, CT scans were performed. Researchers observed that cases exhibited a significantly higher incidence of partial response rate compared with controls (27% vs 7%; OR: 0.3, P < 0.0001). They also found stable disease in 51% of cases and 53% of controls, and progressive disease in 22% and 40%, respectively.

Upon performing multiple logistic regression, the following were found to be not independently associated with the likelihood of achieving partial response: age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, and different salvage chemotherapy regimens.

“At this point we can only speculate on the reasons for better response in those pre-treated with checkpoint inhibitors,” said Dr. Rothschild. “Probably the activation of the immune system by checkpoint inhibition might render tumor cells more sensitive to chemotherapy. Or chemotherapy may help the tumor-specific T-cells to enter the tumor microenvironment and to exert their function.”

He added that they are currently continuing investigation of response duration and toxicity, cautioning that their findings should undergo further research in larger, prospective cohorts.

Marina Garassino, MD, Head of Thoracic Medical Oncology, National Cancer Institute of Milan (Fondazione IRCCS Istituto Nazionale dei Tumori), was enthusiastic about the potential implications of these results, and offered the following comment on the study:

“This is the first research suggesting that chemotherapy could potentially work better after immunotherapy,” she said. “All of us treating patients with immunotherapy have had a feeling about this because we’ve seen unexpected results with some patients, but this is the first study in which this phenomenon is formally described. Although the results are very preliminary, they suggest that immunotherapy can change the natural history of the disease and the micro-environment of the tumor, therefore rendering it more sensitive to chemotherapy. This could potentially point to new areas of research and new sequences of treatment.”

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