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Pretreatment of NSCLC with checkpoint inhibitors improves response to salvage chemotherapy
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Patients with advanced non–small cell lung cancer more often achieved partial response if pretreated with a PD-1/PD-L1 checkpoint inhibitor prior to salvage chemotherapy, according to retrospective study results presented at the European Lung Cancer Conference.
Immune checkpoint inhibitors appear active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy.
“Checkpoint inhibitors are currently the standard of care for NSCLC patients in the second-line setting after chemotherapy and are used for a subset of patients with high PD-L1 expression as frontline therapy,” Sacha Rothschild, MD, PhD, from the division of oncology at University Hospital Basel in Switzerland, said in a press release. “So far, it is unclear how to treat patients not responding to immune checkpoint inhibitors or progressing after initial response to these agents.”
Rothschild and colleagues evaluated responses in 82 patients (men, n = 46) with stage IV NSCLC who received salvage chemotherapy alone or after PD-1/PD-L1 inhibitors. The analysis included patients with adenocarcinoma (n = 63), squamous cell carcinoma (n = 18) and one case of large cell carcinoma.
Sixty-seven patients received PD-1/PD-L1 inhibitors — either nivolumab (Opdivo, Bristol-Myers Squibb; n = 56), pembrolizumab (Keytruda, Merck; n = 7) or atezolizumab (Tecentriq, Genentech; n = 4) — and 15 controls received salvage chemotherapy alone.
Patients in the checkpoint inhibitor group had received more chemotherapy regimens prior to salvage chemotherapy than controls (mean, 2.37 vs. 1.93).
Salvage chemotherapy included docetaxel (62%), pemetrexed (20%), gemcitabine (12%) and paclitaxel (6%).
Control patients demonstrated a lower partial response rate than those in the PD-1/PD-L1 treatment group (7% vs. 27%; OR = 0.3; 95% CI, 0.18-0.5).
A smaller proportion patients treated with checkpoint inhibitors than controls experienced progressive disease (22% vs. 40%), although rates of stable disease appeared comparable (51% vs. 53%).
“Our results are of utmost importance for NSCLC patients,” Rothschild said. “The activity of conventional chemotherapy in this setting has not been investigated so far. Therefore, these results are good news for patients [who] progress after immunotherapy and are still fit enough to receive further palliative therapy.”
Multiple logistic regression showed no independent association between age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, or different salvage chemotherapy regimens and the likelihood of achieving partial response.
“At this point we can only speculate on the reasons for better response in those pretreated with checkpoint inhibitors,” Rothschild said. “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.”
Rothschild noted investigations are ongoing to evaluate duration of response and toxicity in this patient population, cautioning that this finding must be further explored in larger and prospective cohorts. – by Kristie L. Kahl
Reference:
Rothschild SI, et al. Abstract 91PD. Presented at: European Lung Cancer Conference; May 5-8, 2017; Geneva, Switzerland.
Disclosures: The researchers report no relevant financial disclosures.