Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment

Tozuka, Takehiro; Kitazono, Satoru; Sakamoto, Hiroaki; Yoshida, Hiroshi; Amino, Yoshiaki; Uematsu, Shinya; Yoshizawa, Takahiro; Hasegawa, Toshiyuki; Ariyasu, Ryo; Uchibori, Ken; Yanagitani, Noriko; Horai, Takeshi; Seike, Masahiro; Gemma, Akihiko; Nishio, Makoto

doi:10.1016/j.lungcan.2020.04.021

Cited by 23 publications

(57 citation statements)

References 19 publications

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“… 22 Very recently, 2 studies from Japan performed a propensity score weighted analysis of R + D after ICI treatment in NSCLC patients to investigate the effect of this sequence in comparison to a control group without PD-1/PD-L1-directed therapy. 23 , 24 While Kato et al described a benefit for the ICI pretreated cohort in terms of ORR, but not for outcome parameters, Tozuka et al in contrast showed a significant increase in PFS, 5.9 months versus 2.8 months (in the control group); P = 0.03, and a trend toward an improved OS for the ICI pretreated cohort. Further details of all mentioned R + D third-line studies are presented in Table 4 .…”

Section: Discussionmentioning

confidence: 98%

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: Discussionmentioning

confidence: 98%

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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“…We and others recently reported excellent PFS and OS data for D+R given in 3rd line immediately after ICI monotherapy (15,(20)(21)(22)(23)(24). We have hypothesized that antiangiogenic agents not only act directly through VEGFmediated effects but also produce synergistic effects with chemotherapeutic agents and ICI agents for instance by contributing to better drug penetration through their action on tumor vessels (15,(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Brueckl¹,

Reck²,

Rittmeyer³

et al. 2021

Transl Lung Cancer Res

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Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations.However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.Methods: Retrospective data were collected during routine care from German thoracic oncology centers.Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint.Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis.Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS

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“…Categorical variables were evaluated using the Fisher’s test and multivariate analysis using the Cox proportional hazards regression. The hazard ratios were also calculated after adjusting for confounding factors including age, gender, smoking status, histology, driver mutation, PD-L1 status, and lung honeycombing with inverse probability of treatment weighting (IPTW) using propensity scores as previously described [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…The comparative clinical trial of DTX/RAM versus placebo/DTX or the REVEL trial showed survival benefits as a second-line treatment of stage IV non-small cell lung cancer (NSCLC) after disease progression on platinum-based therapy [ 7 ]. Recent studies have also revealed the efficacy of the DTX/RAM combination therapy in patients with a history of ICI treatment [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Although the combination of chemotherapy and ICIs is currently becoming the standard regimen as the first-line treatment of advanced NSCLC, there is an insufficient number of studies regarding the use of chemotherapy and ICI combination as a second-line or later-line therapy.…”

Section: Introductionmentioning

confidence: 99%

Is the Efficacy of Adding Ramucirumab to Docetaxel Related to a History of Immune Checkpoint Inhibitors in the Real-World Clinical Practice?

Nishimura

Fujimoto

Okano

et al. 2022

Cancers

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Reports on the efficacy of second-line treatment with cytotoxic agents after treatment with immune checkpoint inhibitors are limited. Here, we retrospectively evaluated patients in the real-world clinical practice treated with docetaxel or docetaxel plus ramucirumab. Ninety-three patients treated with docetaxel or docetaxel plus ramucirumab as a second- or later-line therapy were included. The patients were categorized into the following four treatment groups: docetaxel group (n = 50), docetaxel/ramucirumab group (n = 43) and pretreated (n = 45) and untreated (n = 48) with immune checkpoint inhibitor groups. The docetaxel/ramucirumab group showed an overall response rate of 57.1% in patients pretreated with immune checkpoint inhibitors and 20% in untreated patients. The docetaxel group showed an overall response rate of 15.4% in patients pretreated with immune checkpoint inhibitors and 5.0% in untreated patients. The median time-to-treatment failure and the median survival time were longer in the docetaxel/ramucirumab group than in the docetaxel group in both immune checkpoint inhibitor-pretreated and -untreated groups. There was no difference in time-to-treatment failure and overall survival between immune checkpoint inhibitor-pretreated and -untreated groups in each docetaxel and docetaxel/ramucirumab treatment group. In conclusion, our real-world data show that the addition of ramucirumab to docetaxel was superior to docetaxel monotherapy for improving time-to-treatment failure and overall survival, irrespective of previous treatment with immune checkpoint inhibitors.

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Addition of ramucirumab enhances docetaxel efficacy in patients who had received anti-PD-1/PD-L1 treatment

Cited by 23 publications

References 19 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

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Is the Efficacy of Adding Ramucirumab to Docetaxel Related to a History of Immune Checkpoint Inhibitors in the Real-World Clinical Practice?

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