Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer

Schvartsman, Gustavo; Peng, Shaohua; Bis, Giorgios; Lee, John; Benveniste, Marcelo Felipe Kuperman; Zhang, Jianjun; Roarty, Emily; Lacerda, Lara; Swisher, Stephen G.; Heymach, John V.; Fossella, Frank V.; William, William N.

doi:10.1016/j.lungcan.2017.07.034

Cited by 195 publications

(179 citation statements)

References 30 publications

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“…Our data indicate that the combination of docetaxel plus ramucirumab as a VEGFR2 inhibitor may contribute to the improved response rate. 4,5 Previous studies suggest that immunotherapy may introduce tumor synergistic effects to subsequent cytotoxic therapy; our results are consistent with this finding . Moreover, it has been reported that therapeutic level of anti‐PD‐1 is maintained when chemotherapy is administered because of the long half‐life of the PD‐1 antibody .…”

Section: Discussionsupporting

confidence: 90%

“…We usually administer cytotoxic agents, such as docetaxel, S‐1, pemetrexed, and ramucirumab plus docetaxel. Recently, Schvartman et al reported that the response rates to single‐agent chemotherapy after exposure to ICIs were higher in 28 patients with advanced NSCLC compared to those in historical controls . In their study, the overall response rate (ORR) of single agents after ICIs was 39%.…”

Section: Introductionmentioning

confidence: 99%

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Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients

et al. 2019

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Background It is unclear whether the chemotherapy response improves after exposure to immunotherapy. Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects that stimulate tumor shrinkage. We conducted a retrospective study to evaluate improvement of the efficacy of ramucirumab plus docetaxel after the failure of nivolumab as a PD‐1 inhibitor. Methods From February 2016 to December 2017, 152 patients with non‐small cell lung cancer (NSCLC) administered nivolumab in our institution were identified. We reviewed the records of 20 NSCLC patients administered ramucirumab plus docetaxel after nivolumab failure. The overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS) were investigated. Pegylated granulocyte colony‐stimulating factor was prophylactically administered to 18 patients (90%) after the administration of ramucirumab plus docetaxel. Results The median age of the patients was 70 (range: 55–77) years. Twelve patients were male and eight were female. The histology was adenocarcinoma in 16 patients, squamous cell carcinoma in three, and other in one. The ORR of ramucirumab plus docetaxel was 60%, and the PFS and OS were 169 and 343 days, respectively. Among the 20 patients, 12 achieved a partial response, giving an ORR of 60.0%. Six patients had stable disease and two had progressive disease. The disease control rate was 90%. Gastrointestinal adverse events were frequently observed in 19 patients. Conclusions Ramucirumab plus docetaxel achieved a higher response rate when administered immediately after nivolumab failure compared to regimens without prior nivolumab administration.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients

et al. 2019

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“…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 .…”

Section: Discussionmentioning

confidence: 99%

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

et al. 2017

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Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab‐refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD‐ligand 1 (PD‐L1)‐expressing cancer cells, accompanied by tumor‐infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM‐3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.

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“…The combination of immunotherapy and chemotherapy, including salvage chemotherapy following PD‐1 inhibitor therapy, is a promising treatment for patients with non‐small cell lung cancer (NSCLC) . We recently reported that salvage chemotherapy following nivolumab increased the response in some patients with NSCLC, regardless of tumor PD‐L1 status .…”

Section: Introductionmentioning

confidence: 99%

Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

et al. 2018

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Several recent studies have shown that salvage chemotherapy following PD‐1 blockade produces high antitumor activity in some patients with non‐small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil‐to‐lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid‐derived suppressor cells and tumor‐associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time‐series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non‐responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non‐responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD‐1 blockade and chemotherapy.

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Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer

Cited by 195 publications

References 30 publications

Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients

Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

Dynamics of blood neutrophil‐related indices during nivolumab treatment may be associated with response to salvage chemotherapy for non‐small cell lung cancer: A hypothesis‐generating study

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