Increased Response Rates to Salvage Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non–Small Cell Lung Cancer

Park, Song Ee; Lee, Se‐Hoon; Ahn, Jin Seok; Ahn, Myung Ju; Park, Keunchil; Sun, Jong Mu

doi:10.1016/j.jtho.2017.10.011

Cited by 219 publications

(208 citation statements)

References 15 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%

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%

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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“…The sequence of chemotherapy following nivolumab improved anti‐tumor activity regardless of tumor PD‐L1 expression, but the reverse sequence did not. Similar to these findings, four retrospective studies of salvage chemotherapy, including a case–control study, showed a high ORR of 38% and median PFS of approximately four months in previously treated patients with NSCLC . In the case–control study, the odds ratio for achieving an objective response to salvage chemotherapy was more than three times higher .…”

Section: Discussionsupporting

confidence: 62%

“…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 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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BackgroundThe combination of PD‐1 inhibitors and cytotoxic drugs is reported to enhance anti‐tumor activity in non‐small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor‐infiltrating immune cells.MethodsThe medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression‐free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab.ResultsEight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4–90.6%; P = 0.004) and median progression‐free survival to six months (95% CI 4.6–7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD‐L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm2 of PD‐1+ immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm2. Responders had fewer PD‐1+ immune cells than non‐responders (percentage P = 0.028; density P = 0.034).ConclusionSalvage chemotherapy following nivolumab improved anti‐tumor activity regardless of tumor PD‐L1 status, but nivolumab following chemotherapy did not. The presence of few PD‐1+ tumor‐infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re‐sensitizes the tumor immune microenvironment to chemotherapy.

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“…This was a retrospective cohort study of patients with advanced‐stage NSCLC who received palliative pembrolizumab. We retrospectively identified 172 patients who received pembrolizumab between July 2014 and January 2018 from the lung cancer immunotherapy registry of Samsung Medical Center, and who had undergone spirometry testing within the past 3 years. Patients with small cell lung cancer ( n = 3), and those who received ICI treatment for an adjuvant purpose ( n = 14), received ICI treatment previously ( n = 7), underwent combined treatment with other types of ICIs ( n = 2), or died within 2 weeks of ICI treatment initiation ( n = 13) were excluded.…”

Section: Methodsmentioning

confidence: 99%

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Shin

Park

et al. 2019

Intl Journal of Cancer

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Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre‐bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression‐free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry‐based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26–0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31–0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry‐defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab.

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Increased Response Rates to Salvage Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non–Small Cell Lung Cancer

Abstract: The ORR for SCAI was significantly higher than that for LCBI. These data indicate that anti-PD-1/PD-L1 inhibitors could make tumors more vulnerable to subsequent chemotherapy.

Cited by 219 publications

References 15 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

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

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

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