Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.

e15007 Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (>1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.

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Best supportive care in combination with polychemotherapy versus best supportive care alone as second-line therapy in stage IV metastatic melanoma (DeCOG MM-PAL 8)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8567 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8567-8567

Author(s):

J. Ulrich ◽

U. Trefzer ◽

W. Tilgen ◽

D. Schadendorf ◽

M. Kaatz ◽

...

Keyword(s):

Overall Survival ◽

Supportive Care ◽

Metastatic Melanoma ◽

Stage Iv ◽

Best Supportive Care ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy

8567 Background: To date, there is no evidence of survival benefit from randomized trials in stage IV metastatic melanoma (MM) after disease progression to first-line therapy. Therefore, we initiated a phase III trial to evaluate the impact on survival of polychemotherapy in patients (pts.) receiving best supportive care (BSC) as second-line therapy. Methods: This prospective multicenter controlled study was conducted by the Dermatologic Cooperative Oncology Group (DeCOG) with 13 participating centers. Pts. with stage IV MM disease between 18 and 75 yrs. and a Karnofsky performance status (KPS) > 60 with progression after first-line chemotherapy or chemo-immunotherapy were offered to choose between polychemotherapy + BSC or BSC alone. Pts. were required to have adequate renal, liver and bone marrow function. The regimen consisted of cisplatin (50 mg/m2), vindesine (3 mg/m2) and dacarbacin (450 mg/m2) given on day 1 and 8 every 28 days (CVD). Reevaluation according to WHO response criteria were performed every 2 cycles. Primary endpoint was the median overall survival (OS). Secondary endpoints were overall response rate (OR) (only CVD arm) and quality of life (QOL). Results: Between 1/02 and 8/06 120 pts. were recruited, a minority of 35 pts. (29%) chose the BSC arm (A) and 85 (71%) the CVD + BSC arm (B). Five pts. were ineligible, and thus 115 pts. treated per protocol. There was a significant lower KPS in arm A at study entry. At the time of data analysis, 85% of the pts. had died from melanoma. There was no siginificant difference (p=0.093) in median OS between the two arms, 9.0 [95% CI: 3,9–14,1] months in arm A and 8.0 [95% CI: 6,5–9,5] months in arm B. The OR in arm B was 7.5% (2 CR, 3 PR). Conclusions: Polychemotherapy (CVD) + BSC as second-line therapy in stage IV MM does not improve overall survival as compared to BSC alone. No significant financial relationships to disclose.

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Phase III Trial of Pemetrexed Plus Best Supportive Care Compared With Best Supportive Care in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.9887 ◽

2008 ◽

Vol 26 (10) ◽

pp. 1698-1704 ◽

Cited By ~ 141

Author(s):

Jacek Jassem ◽

Rodryg Ramlau ◽

Armando Santoro ◽

Wolfgang Schuette ◽

Assad Chemaissani ◽

...

Keyword(s):

Partial Response ◽

Supportive Care ◽

Malignant Pleural Mesothelioma ◽

Cox Regression ◽

Progression Free Survival ◽

Best Supportive Care ◽

Phase Iii ◽

Pleural Mesothelioma ◽

Second Line ◽

First Line

PurposeThis multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free survival (PFS), time to tumor progression (TTP), time to treatment failure (TTF), and toxicity.Patients and MethodsPatients with relapsed MPM after first-line chemotherapy were randomly assigned to receive pemetrexed 500 mg/m2plus BSC (P+BSC) every 21 days or BSC alone.ResultsThe study enrolled 243 patients (123 on P+BSC arm and 120 on BSC arm). Median OS time was not significantly different between the arms (8.4 months for P+BSC and 9.7 months for BSC; P = .74). Cox regression modeling suggested a trending survival benefit for patients who responded to first-line therapy. Time-to-event measures significantly favored P+BSC (median PFS, TTP, and TTF). Partial response was achieved in 18.7% and 1.7% of patients in P+BSC and BSC arms, respectively (P < .0001), and a disease control rate (partial response plus stable disease) was achieved in 59.3% and 19.2% of patients in P+BSC and BSC arms, respectively (P < .0001). Use of postdiscontinuation chemotherapy was significantly greater among BSC patients compared with P+BSC patients (51.7% v 28.5%, respectively; P = .0002), with more BSC patients receiving pemetrexed (18.3% v 3.3%, respectively; P = .0001). Postdiscontinuation therapy was initiated earlier for BSC than P+BSC patients (median time to initiation, 4.3 v 15.7 months, respectively; log-rank P < .0001). Chemotherapy was well tolerated, with expected modest (4% to 7%) grade 3 and 4 hematologic toxicities.ConclusionSecond-line pemetrexed elicited significant tumor response and delayed disease progression compared with BSC alone in patients with advanced MPM. Improvement in OS was not seen in this study, possibly because of the significant imbalance in postdiscontinuation chemotherapy between the arms.

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Survival effects of a strategy favoring second-line multimodal treatment compared to supportive care in glioblastoma patients at first progression

Journal of Neurosurgery ◽

10.3171/2018.7.jns18228 ◽

2019 ◽

Vol 131 (4) ◽

pp. 1136-1141

Author(s):

Pantelis Stavrinou ◽

Aristotelis Kalyvas ◽

Stefan Grau ◽

Christina Hamisch ◽

Norbert Galldiks ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Supportive Care ◽

Treatment Strategy ◽

Multimodal Treatment ◽

Therapeutic Modality ◽

Line Treatment ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy

OBJECTIVEData on the survival effects of supportive care compared to second-line multimodal treatment for glioblastoma progression are scarce. Thus, the authors assessed survival in two population-based, similar cohorts from two European university hospitals with different treatment strategies at first progression.METHODSThe authors retrospectively identified patients with newly diagnosed glioblastoma treated at two neurooncological centers. After diagnosis, patients from both centers received identical treatments, but at tumor progression each center used a different approach. In the majority of cases, at center A (Greece), supportive care or a single therapeutic modality was offered at progression, whereas center B (Germany) provided multimodal second-line therapy. The main outcome measure was survival after progression (SaP). The influence of the treatment strategy on SaP was assessed by multivariate analysis.RESULTSOne hundred three patients from center A and 156 from center B were included. Tumor progression was observed in 86 patients (center A) and 136 patients (center B). At center A, 53 patients (72.6%) received supportive care alone, while at center B, 91 patients (80.5%) received second-line treatment. Progression-free survival at both centers was similar (9.4 months [center A] vs 9.0 months [center B]; p = 0.97), but SaP was significantly improved in the patients treated with multimodal second-line therapy at center B (7 months, 95% CI 5.3–8.7 months) compared to those treated with supportive care or a single therapeutic modality at center A (4.5 months, 95% CI 3.5–5.5 months; p = 0.003). In the multivariate analysis, the treatment center was an independent prognostic factor for overall survival (HR 1.59, 95% CI 0.17–2.15; p = 0.002).CONCLUSIONSTreatment strategy favoring multimodal second-line treatment over minimal treatment or supportive care at glioblastoma progression is associated with significantly better overall survival.

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Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma

PLoS ONE ◽

10.1371/journal.pone.0184423 ◽

2017 ◽

Vol 12 (9) ◽

pp. e0184423 ◽

Cited By ~ 27

Author(s):

Billy Amzal ◽

Shuai Fu ◽

Jie Meng ◽

Johanna Lister ◽

Helene Karcher

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Supportive Care ◽

Renal Cell ◽

Meta Analysis ◽

Progression Free Survival ◽

Best Supportive Care ◽

Line Treatment ◽

Second Line ◽

Free Survival

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Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

Journal of Clinical Oncology ◽

10.1200/jco.2004.11.037 ◽

2004 ◽

Vol 22 (7) ◽

pp. 1209-1214 ◽

Cited By ~ 761

Author(s):

Axel Grothey ◽

Daniel Sargent ◽

Richard M. Goldberg ◽

Hans-Joachim Schmoll

Keyword(s):

Colorectal Cancer ◽

Advanced Colorectal Cancer ◽

Cytotoxic Agents ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

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DERN CONTROL POINT INHIBITORS AND THEIR POSSIBILITIES FOR THE THERAPY OF METASTATIC UROTELIAL CANCER

EurasianUnionScientists ◽

10.31618/esu.2413-9335.2020.6.74.761 ◽

2020 ◽

Vol 6 (5(74)) ◽

pp. 4-8

Author(s):

M.N. Tillyashajhov ◽

S.V. Kamyshov ◽

E.V. Bojko

Keyword(s):

Overall Survival ◽

Control Point ◽

Surface Protein ◽

New Drugs ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Critical Question ◽

Accelerated Approval ◽

New Biomarkers

For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC). Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T‑lymphocytes PD‑1 and its ligands PD‑L1 and PD‑L2, resulting in the activation of the immune response. It is noteworthy that the anti‑PD‑1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA). Nivolumab (antibody PD‑1) also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD‑L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first‑line treatment in patients not receiving cisplatin). Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation.The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.

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Evaluation of second line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first line cediranib

Canadian Urological Association Journal ◽

10.5489/cuaj.2426 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 398 ◽

Cited By ~ 3

Author(s):

Suzanne Richter ◽

Jo-An Seah ◽

Gregory R Pond ◽

Hui K Gan ◽

Mary J. Mackenzie ◽

...

Keyword(s):

Renal Cell ◽

Kinase Inhibitor ◽

Cell Cancer ◽

Phase Iii ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Pivotal Phase ◽

Line Therapy ◽

To Receive

Introduction: Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.Methods: In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.Results: Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%–47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.Conclusion: In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.

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Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Oncology ◽

10.1159/000509387 ◽

2020 ◽

Vol 98 (11) ◽

pp. 787-797 ◽

Cited By ~ 2

Author(s):

Yuwa Ando ◽

Tomokazu Kawaoka ◽

Yosuke Suehiro ◽

Kenji Yamaoka ◽

Yumi Kosaka ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Liver Function ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Class A ◽

Line Therapy ◽

Pugh Class ◽

Ecog Ps

Background: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. Methods: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. Results: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, p = 0.01) were significant prognostic factors. Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

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