Response to salvage chemotherapy following exposure to immune checkpoint inhibitors in patients with non-small cell lung cancer.

Abstract

9084 Background: Immune checkpoint inhibitors are active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy. We evaluated responses to chemotherapy in patients who had progressed on a checkpoint inhibitor. Methods: Eligible patients were adults with NSCLC who received salvage chemotherapy following PD-1/PD-L1 inhibitors (cases) versus no PD-1/PD-L1 inhibitors (controls). CT-imaging was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response. Results: Three-hundred and fifty patients’ charts were reviewed and 82 patients met eligibility criteria. Among evaluable patients, 46 were males. Sixty-seven patients were cases versus 15 controls. Fifty-six patients received nivolumab, 7 pembrolizumab and 4 atezolizumab. Sixty-three (77%) had adenocarcinoma, 18 (22%) squamous cell carcinoma and 1 (1%) large cell carcinoma. The mean number of chemotherapy regimens prior to salvage chemotherapy was 2.37 (95% C.I. 2.10-2.64)) in cases versus 1.93 (95% C.I: 1.32-2.54) in controls. Salvage drugs included docetaxel (62%), pemetrexed (20%), gemcitabine (12%), paclitaxel (6%). Eighteen (27%) cases had partial response to chemotherapy versus 1(7%) controls. Fifteen (22%) cases had progressive disease versus 6 (40%) controls. Thirty-four (51%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.30 (95% CI: 0.18 to 0.50, P = 0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response. Conclusions: The odds of achieving a partial response to salvage chemotherapy were more than 3 times higher inpatients with prior exposure to PD-1/PD-L1 inhibitors. Ongoing investigations include the duration of response as well as evaluation of toxicity.

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

“…Third‐line cytotoxic chemotherapy has been reported to have a low response rate of 3–9% . Recently, three retrospective studies, including a case–control study, presented a promising response rate of 25–39% after salvage chemotherapy following exposure to PD‐1/PD‐L1 inhibitors (Table ) . The case–control study revealed an odds ratio of 0.30 (95% confidence interval 0.18–0.50) for achieving a partial response to salvage chemotherapy .…”

“…Recently, three retrospective studies, including a case–control study, presented a promising response rate of 25–39% after salvage chemotherapy following exposure to PD‐1/PD‐L1 inhibitors (Table ) . The case–control study revealed an odds ratio of 0.30 (95% confidence interval 0.18–0.50) for achieving a partial response to salvage chemotherapy . In phase I/II trials, concurrent administration of the PD‐1 inhibitor with first‐line chemotherapy showed a high response rate of > 50% .…”

Presence of few PD‐1‐expressing tumor‐infiltrating immune cells is a potential predictor of improved response to salvage chemotherapy following nivolumab for non‐small cell lung cancer: An exploratory case series

“…We have reported the drastic regression of lung cancer cases treated with chemotherapy following nivolumab, which is known as salvage chemotherapy . Several recent studies have also shown that the combination therapy of PD‐1 inhibitors with anti‐cancer drugs, including salvage chemotherapy, produces high anti‐tumor activity in some patients . Salvage chemotherapy showed a high objective response rate of 38% (95% confidence interval [CI] 31.3–44.7%) in a total of 200 cases obtained from four retrospective studies …”

First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma

“…In support of this, patients with NSCLC who were randomized to front‐line pembrolizumab followed by investigator‐choice cytotoxic therapy, which was paclitaxel in 19% of patients, had a longer time to progression after the initiation of second‐line therapy compared with patients randomized to front‐line cytotoxic therapy followed by investigator‐choice therapy, which usually consisted of PD‐1 blockade (KEYNOTE‐024) . A similar pattern was observed in a separate NSCLC study, which showed that salvage chemotherapy was associated with a response rate of 27% among patients with prior exposure to PD‐1/PD‐L1 inhibitors versus 7% without prior exposure .…”

“…Recent data from non‐small cell lung cancer (NSCLC) suggest that anti‐PD‐1 therapy may enhance sensitivity to subsequent chemotherapy . To date, reports on treatment efficacy after failure of PD‐1 blockade in advanced gastroesophageal adenocarcinoma are lacking.…”