Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy

Harada, Daijiro; Takata, Kazuyuki; Mori, Shunta; Kozuki, Toshiyuki; Takechi, Yoshizumi; Moriki, Satoko; Asakura, Yumi; Ohno, Takamasa; Nogami, Naoyuki

doi:10.21873/anticanres.13688

Cited by 46 publications

(95 citation statements)

References 12 publications

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“… 16 While this registration trial showed a median PFS of 4.5 months for this combination, our cohort showed a median PFS of 6.8 months and a DOR of 10.2 months. A similar observation has previously been demonstrated in a small retrospective analysis by Harada et al 18 This group reported a median PFS of 5.7 months with a sequence of ICI followed by R + D in contrast to 2.3 months with R + D followed by ICI ( P = 0.020). Our data are also in line with another small study from Japan reporting a median PFS of 5.9 months using R + D after ICI.…”

Section: Discussionsupporting

confidence: 86%

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

Brückl

Reck

Rittmeyer³

et al. 2020

Clin Med Insights Oncol

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Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

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Section: Discussionsupporting

confidence: 86%

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

Brückl

Reck

Rittmeyer³

et al. 2020

Clin Med Insights Oncol

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“…Grade 1 or 2 diarrhoea or stomatitis were also more frequent in the anti-PD-1-exposed group than the anti-PD-1-naïve group among patients with taxanes plus RAM, consistent with the safety profiles of docetaxel plus RAM before and after PD-1 therapy in NSCLC, or in a phase II study of nivolumab combined with PTX plus RAM. 19 30 Further analysis with a large sample size as well as pretreatment and post-treatment biopsies is thus essential to clarify the immunological effect of taxanes plus RAM after PD-1 therapy on such toxicities.…”

Section: Discussionmentioning

confidence: 99%

Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer

Sasaki¹,

Kawazoe²,

Eto³

et al. 2020

ESMO Open

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BackgroundThe efficacy and safety of chemotherapy (CTx) after anti-PD-1 therapy in patients with advanced gastric cancer (AGC) remains unclear.MethodsMedical records of consecutive patients with AGC treated with both CTx (taxanes plus ramucirumab, taxanes monotherapy or irinotecan) and anti-PD-1 therapy from June 2015 to April 2019 were retrospectively analysed. Patients were divided into two groups based on prior exposure to anti-PD-1 therapy: anti-PD-1-exposed and anti-PD-1-naïve groups. CTx-related outcomes were compared between two groups in the overall population and each CTx population.ResultsIn total, 233 patients (67 anti-PD-1-exposed, 166 anti-PD-1-naïve) were included. In the overall population, the objective response rate (ORR) to CTX was 44.6% in the anti-PD-1-exposed group and 19.6% in the anti-PD-1-naïve group (p=0.001); the median progression-free survivals (PFS) were 3.7 months and 3.3 months (HR=0.82, p=0.20), respectively. Among patients receiving taxanes plus ramucirumab (n=149), ORR (60.6% vs 20.0%, p<0.001) and median PFS (4.8 vs 3.4 months, p=0.004, HR=0.56) were significantly better in the anti-PD-1-exposed group (n=39) compared with the anti-PD-1-naïve group (n=110). These differences were not observed in patients receiving taxane monotherapy (n=34) or irinotecan (n=50). CTx after anti-PD-1 therapy showed no severe or unexpected adverse events.ConclusionsPrior anti-PD-1 therapy might increase tumour response to taxanes plus ramucirumab without unexpected adverse events, which warrants further investigations in a large cohort.

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“…The other mechanism is the combination of cytotoxic and antiangiogenic agents resulting in an intensified ICI treatment effect . However, Harada et al reported that docetaxel and ramucirumab chemotherapy after ICI treatment induced ILD in three out of 18 patients . Although CT findings showed similar diffuse GGO in our three patients, we could not obtain pathological specimens and the aetiology remains unclear.…”

Section: Discussionmentioning

confidence: 56%

“…Although the mechanisms underlying the association are unknown, nivolumab has been thought to successfully activate the host immune system. On the other hand, chemotherapy with docetaxel and ramucirumab after ICI treatment was reported to show high efficacy compared to that noted in cases without the previous use of ICI treatment . It has been suggested that the high efficacy of docetaxel and ramucirumab after ICI treatment is attributable to the following two mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…The first mechanism is alteration of the tumour and/or microenvironment by ICI treatment resulting in increased sensitivity to cytotoxic agents. The other mechanism is the combination of cytotoxic and antiangiogenic agents resulting in an intensified ICI treatment effect . However, Harada et al reported that docetaxel and ramucirumab chemotherapy after ICI treatment induced ILD in three out of 18 patients .…”

Section: Discussionmentioning

confidence: 99%

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Interstitial lung disease induced by docetaxel and ramucirumab chemotherapy after nivolumab treatment

Okeya

Kawagishi

Yamoto

et al. 2020

Respirology Case Reports

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Three men (aged 64, 65, and 67 years) with advanced lung cancer who had been treated with nivolumab developed interstitial lung disease (ILD) during chemotherapy with docetaxel and ramucirumab. The treatment was clinically effective; however, the patients experienced immune-related adverse effects due to nivolumab therapy: two patients developed ILD and the third developed psoriasis. Because the patients showed progression, docetaxel and ramucirumab chemotherapy was administered. Although two patients showed a clinical response, all patients developed grade 3 ILD during therapy. Furthermore, the patients developed respiratory failure and needed corticosteroid therapy. Although their condition improved owing to the therapy, the patients could not receive additional cancer treatment and died of cancer. On the basis of the results obtained, we speculated that although the regimen of docetaxel and ramucirumab after nivolumab therapy might be effective against non-small cell lung cancer, it might increase the risk for ILD in some patients.

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Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy

Cited by 46 publications

References 12 publications

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV

Improved efficacy of taxanes and ramucirumab combination chemotherapy after exposure to anti-PD-1 therapy in advanced gastric cancer

Interstitial lung disease induced by docetaxel and ramucirumab chemotherapy after nivolumab treatment

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