GENEVA (FRONTLINE MEDICAL NEWS) – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.

In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.

“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.

Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.

Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.

Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.

Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.

As noted, 18 cases but only 1 control patient had a partial response to salvage chemotherapy. The rates of stable disease in cases and controls, respectively, were 51% (34 patients) and 53% (8 patients). However, only 22% of controls (15 patients) had progressive disease, compared with 40% of controls (6 patients).

The odds ratio for achieving a partial response was 0.30 (95% confidence interval, 0.18-0.50, P less than .0001).

In a multiple logistic regression model, neither age, sex, number of prior chemotherapy regimens, tumor histology, smoking status, nor type of salvage chemotherapy regimen were significantly associated with the likelihood of achieving a partial response.

In a poster discussion session, Simon Ekman, MD, of Karolinska Institute in Stockholm, Sweden, the invited discussant, said that the data from the study are convincing, and raise the question of what to do next.

“The question is how do we combine immunotherapy with chemotherapy? Should we use the immune therapy first, like in this trial, or vice versa, or should we combine concurrently” he said.

The strategy of chemotherapy first is supported by research showing that neoantigens crucial for the immune response are released during chemotherapy and radiotherapy, enabling immunotherapeutic agents to work better, he said.

The study was internally funded. Dr. Rothschild and Dr. Ekman reported no conflicts relevant to the research.


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