Unexpected response to cisplatin rechallenge after immune checkpoint inhibitors in patients with metastatic urothelial carcinoma refractory to platinum regimen

Gravis, Gwénaëlle; Billon, Emilien; Baldini, Capucine; Massard, Christophe; Hilgers, Werner; Delva, R.; Walz, Jochen; Pignot, G.; Rybikowski, S.; Dermeche, Slimane; Thomassin, Jeanne; Brunelle, Serge; Lavaud, Pernelle; Loriot, Yohann

doi:10.1016/j.ejca.2018.09.002

Cited by 18 publications

(26 citation statements)

References 5 publications

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“…Similar data have been previously reported both in urothelial and lung cancer, suggesting that the sequence of immunotherapy followed by chemotherapy might be better than the opposite, at least in terms of response. 20 , 21 …”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Bersanelli

Buti

Cortellini

et al. 2021

Clin Med Insights Oncol

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Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment ( p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

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Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Bersanelli

Buti

Cortellini

et al. 2021

Clin Med Insights Oncol

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“…However, unexpected effects have been reported in cases of further treatment after ICIs in various carcinomas, with chemotherapy as well as molecular-targeted therapy reported to demonstrate marked e cacy in this setting [13][14][15][16]. Unexpected responses to cisplatin rechallenge after treatment with ICIs have been also reported in patients with metastatic UC refractory to platinum regimens [17]. Therefore, avoiding the excessive continuation of rst-line platinum-based chemotherapy may be an important strategy from the perspective of performing salvage chemotherapy after platinum-based chemotherapy and pembrolizumab.…”

Section: Discussionmentioning

confidence: 97%

Optimal Timing of Sequencing From Platinum-based Chemotherapy to Pembrolizumab for Advanced Urothelial Carcinoma Based on Real-World Data: A Multi-Institutional Retrospective Study

Furubayashi

Morokuma

Tomoda

et al. 2020

Preprint

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BackgroundTo evaluate the optimal timing of sequencing from platinum-based chemotherapy to pembrolizumab with advanced urothelial carcinoma (UC) in real-world clinical practice.MethodsA total of 34 patients who received pembrolizumab as second-line treatment after first-line platinum-based chemotherapy for advanced UC at 4 institutions between January 2018 and August 2020 were retrospectively evaluated.ResultsThe gemcitabine and cisplatin regimen was administered to 27 patients (79.4%), and the gemcitabine and carboplatin regimen was administered to 6 patients (20.6%). Regarding the number of chemotherapy cycles administered before pembrolizumab, ≤4 cycles were administered to 22 patients (64.7%), 5-6 cycles to 4 patients (11.8%) and ≥7 cycles to 8 patients (23.5%). When the number of cycles was divided into 4 courses, the median overall survival (OS) for ≤4 and >4 prior chemotherapy cycles was 7.0 months and 25.5 months, respectively (P=0.034). When the number of cycles was divided into 6 courses, the median OS for ≤6 and >6 prior chemotherapy cycles was 11.3 months and 6.6 months, respectively (P=0.658). Multivariate analyses for the OS of pembrolizumab revealed that the Eastern Cooperative Oncology Group Performance Status (≥2: hazard ratio [HR] 9.994, 95% CI=1.854-53.879, P=0.007), liver metastases (positive: HR 3.751, 95% CI=0.958-13.603, P=0.047) and time from previous chemotherapy (≥3 months: HR 0.094, 95% CI=0.023-0.357, P<0.001) were independent prognostic factors, but the number of chemotherapy cycles before pembrolizumab was not an independent prognostic factor. When the number of cycles was divided into 4 courses, the median OS from the first-line treatment with ≤4 and >4 prior chemotherapy cycles was 17.3 months and 37.1 months, respectively (P<0.001). When the number of cycles was divided into 6 courses, the median OS from the first-line treatment for ≤6 and >6 prior chemotherapy cycles was 18.6 months and 27.3 months, respectively (P=0.276).ConclusionsThese real-world findings suggest that the optimal timing of sequencing from platinum-base chemotherapy to pembrolizumab in advanced UC is around six cycles, even if no exacerbations are observed with first-line chemotherapy.

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“…[12][13][14][15] Unexpected responses to cisplatin rechallenge after treatment with immune checkpoint inhibitors have been also reported in patients with metastatic UC refractory to platinum regimens. 7 Since metastatic UC has a severe prognosis (patients tend to have a poor PS, and most die after second-line treatment), resulting in insufficient time to assess the therapeutic effect of re-administration of the same regimen, another regimen chemotherapy is typically selected at our institution. In our previous study, we reviewed the efficacy of TC therapy as a second-line regimen for metastatic UC showing resistance to GC chemotherapy as a first-line chemotherapy regimen.…”

Section: Discussionmentioning

confidence: 99%

“…There are still few reports describing the response to chemotherapy after immune checkpoint inhibition in metastatic UC. [6][7][8] Furthermore, to our knowledge, there are no published studies describing the organ-specific therapeutic effect of chemotherapy when administered in the setting of progression on chemotherapy and immune checkpoint inhibitor in metastatic UC.…”

Section: Introductionmentioning

confidence: 99%

<p>Organ-Specific Therapeutic Effect of Paclitaxel and Carboplatin Chemotherapy After Platinum-Based Chemotherapy and Pembrolizumab for Metastatic Urothelial Carcinoma</p>

Furubayashi

Negishi

Miura

et al. 2020

RRU

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Background: To evaluate the organ-specific therapeutic effect of paclitaxel and carboplatin (TC) chemotherapy in patients who failed platinum-based chemotherapy and pembrolizumab for metastatic urothelial carcinoma (UC). Patients and Methods: We retrospectively reviewed the data of patients with metastatic UC who had received TC chemotherapy after the failure of platinum-based chemotherapy and pembrolizumab. The RECIST 1.1 criteria were used to assess the objective response to pembrolizumab and TC chemotherapy at tumor sites. Results: We analyzed 8 patients (male, n=5; female, n=3; median age, 65 years old). All patients except one had visceral metastasis. The median overall survival for TC was 10.9 months (95% confidence interval, 1.0-12.7 months), and the objective response rate was 25.0% (partial response [PR]: 2 cases). The metastatic organs were the lymph nodes in 5 cases (number of tumor sites: 8), lung in 4 cases (number of tumor sites: 12), liver in 3 cases (number of tumor sites: 14), bone in 3 cases (number of tumor sites: 12), and primary lesion in 3 cases (number of tumor sites: 3). There were no cases of a complete response or progressive disease in any metastatic organs due to TC chemotherapy. A PR was seen in 2 cases of lymph node metastasis (40.0%), 2 cases of lung metastasis (50.0%), and 2 cases of liver metastasis (66.7%). All 3 cases of bone metastasis showed stable disease, as did all 3 cases of primary lesion. Improvement in the therapeutic effect of TC chemotherapy compared with pembrolizumab was observed in 2 cases (40.0%) of lymph node metastasis, 2 cases (50.0%) of lung metastasis, and 1 case (33.3%) of liver metastasis. Conclusion: Lymph node, lung, and liver metastases may respond to TC chemotherapy, even if exacerbated with pembrolizumab after platinum-based chemotherapy in metastatic UC.

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Unexpected response to cisplatin rechallenge after immune checkpoint inhibitors in patients with metastatic urothelial carcinoma refractory to platinum regimen

Cited by 18 publications

References 5 publications

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

Optimal Timing of Sequencing From Platinum-based Chemotherapy to Pembrolizumab for Advanced Urothelial Carcinoma Based on Real-World Data: A Multi-Institutional Retrospective Study

<p>Organ-Specific Therapeutic Effect of Paclitaxel and Carboplatin Chemotherapy After Platinum-Based Chemotherapy and Pembrolizumab for Metastatic Urothelial Carcinoma</p>

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