Impact of hemoglobin level on the outcome of advanced non-small-cell lung cancer (NSCLC) treated with cisplatin and gemcitabine

17010 Background: Negative impact of anemia on survival has been described in NSCLC patients (pts) treated with radiotherapy (RT) or concurrent radiochemotherapy, but scarcely data exist in NSCLC treated with chemotherapy (CT). PURPOUSE: To evaluate the prognosis value of baseline hemoglobin (Hb) among pts with advanced NSCLC treated with cisplatin and gemcitabine. Methods: 433 pts included in two trials conducted by the Spanish Lung Cancer Group (176 pts from the arm A of a randomized phase III trial comparing 3 regimens of CT and 257 pts from a phase II trial) were included in this analysis. No significant differences in baseline characteristics, response and survival (median 8.73 and 9.87 months, p=0.46) were observed between pts of the two trials. The baseline Hb and other potential risk factors for survival were analyzed with Cox Proportional Hazards model in an univariate an multivariate analysis. Results: Stage IIIB with positive pleural effusion (25%), stage IV (75%). 85% had ECOG PS 0–1. Median age: 60 years (range 31–82). 89% male. Histology: 41% adenocarcinoma, 39% squamous cell, 6.5% large cell, 14.5% NSCLC not otherwise specified. Median number of cycles received was 4 (range 1–8). Mean Hb level prior CT was 13.2 g/dl (range 8 to 19.6 g/dl). Response rate was 41% and median survival was 9.57 months (95% CI: 8.57–11–57). No statistically differences in survival were observed by stage (IIIB vs IV), age and gender. In the univariate analysis, number of cycles received (≤3 vs. >3 cycles), ECOG (2 vs 0–1), response (SD+PD vs CR+PR), baseline Hb (≤11 vs >11 gr/dl); minimum Hb during the CT (<10 vs ≥10) and second line CT (No vs Yes) emerged as prognostic factors for survival and were introduced in the multivariate model (see Table ). Conclusions: Hb level at the initiation of CT is an independent prognostic factor of survival this homogenous group of advanced NSCLC treated with cisplatin and gemcitabine. Baseline Hb should be considered as prognosis factor for survival in addition to ECOG. [Table: see text] No significant financial relationships to disclose.

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Final overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7559 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7559-7559 ◽

Cited By ~ 4

Author(s):

Yan Sun ◽

Yuankai Shi ◽

Li Zhang ◽

Xiaoqing Liu ◽

Caicun Zhou ◽

...

Keyword(s):

Overall Survival ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Significant Difference ◽

Biomarker Analysis ◽

Nsclc Patients

7559 Background: A total of 399 pretreated patients with advanced NSCLC were randomly assigned to receive gefitinib or icotinib in the phase III ICOGEN trial, the first head-to-head phase III trial of EGFR-TKIs. The results of the primary endpoint, PFS, have been reported previously. This report represents the final OS and biomarker analysis results. Methods: EGFR mutation was evaluated by using Scorpion ARMS (QIAGEN, n=152). Overall survival was analyzed by Cox proportional-hazards model analysis at 82% maturity. Results: Median OS was 13.3 months for icotinib and 13.9 months for gefitinib (hazard ratio [HR] = 0.90; 95% CI, 0.79 to 1.02; P = .109). The EGFR mutation rate was 43% in the icotinib group and 59% in the gefitinib group. Compared to wild type patients, patients with EGFR mutation had longer PFS (median, 6.2m vs. 2.3m; P=.00001) as well as OS (median, 20.5m vs. 7.7m; P=.00001). There were no significant differences in PFS or OS between the two treatment groups in EGFR mutation-positive subgroup (median PFS, 7.8m vs. 5.3m for icotinib and gefitinib, respectively, P =.3162; median OS, 20.9m vs. 20.2m for icotinib and gefitinib, respectively, P =.7611.) or in EGFR mutation-negative subgroup (median PFS, 2.3m vs. 2.2m for icotinib and gefitinib, respectively, P =.1531; median OS, 7.8m vs. 6.9m for icotinib and gefitinib, respectively, P =.7885.). Conclusions: There is no statistically significant difference between icotinib and gefitinib in PFS or OS when given to NSCLC patients. This suggests that icotinib can provide similar OS benefits to gefitinib in advanced NSCLC patients. Moreover, EGFR mutation status is the strongest predictor in identifying which patients are most likely to benefit from icotinib.

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Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21579 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21579-e21579

Author(s):

Kartik Sehgal ◽

Ritu R. Gill ◽

Poorva Bindal ◽

Anita Geevarghese Koshy ◽

Danielle C McDonald ◽

...

Keyword(s):

Proportional Hazards ◽

Advanced Nsclc ◽

Proportional Hazards Model ◽

Smoking Status ◽

Performance Status ◽

Objective Response ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

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Avelumab (Ave) first-line (1L) maintenance plus best supportive care (BSC) versus BSC alone for advanced urothelial carcinoma (UC): JAVELIN Bladder 100 subgroup analysis based on duration and cycles of 1L chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.438 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 438-438

Author(s):

Yohann Loriot ◽

Thomas Powles ◽

Miguel Ángel Climent Durán ◽

Srikala S. Sridhar ◽

Joaquim Bellmunt ◽

...

Keyword(s):

Proportional Hazards Model ◽

Locally Advanced ◽

Dose Intensity ◽

The United States ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Significant Treatment ◽

Number Of Cycles ◽

To Receive

438 Background: Avelumab 1L maintenance is approved in the United States for patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy based on significantly prolonged overall survival (OS) vs BSC seen in the phase III JAVELIN Bladder 100 trial (NCT02603432). However, optimal duration of 1L chemotherapy is unknown and some patients are unable to receive 6 cycles. We report a post hoc analysis of efficacy by duration or number of cycles of 1L chemotherapy. Methods: Eligible patients with unresectable locally advanced or metastatic UC that had not progressed with 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin were randomized to receive maintenance avelumab + BSC or BSC alone within 4-10 weeks. Subgroups were defined by quartiles (Qs) for duration (<Q1 [<15.0 weeks], Q1-Q2 [15.0 to <18.0 weeks], Q2-Q3 [18.0 to <20.1 weeks], and >Q3 [>20.1 weeks]) or estimated number of cycles (4, 5, or 6) of 1L chemotherapy. Duration of chemotherapy included dosing delays/interruptions, and the decision to stop 1L chemotherapy was at the investigator’s discretion. Treatment arms were compared using an unstratified Cox proportional hazards model for OS. The potential impact of baseline characteristics on treatment patterns or dose intensity was not explored. Results: Numbers of patients in 1L chemotherapy subgroups were generally well balanced between arms (Table). An OS benefit was observed for avelumab + BSC vs BSC alone across subgroups with differing durations or cycles of 1L chemotherapy (Table). A progression-free survival benefit was also observed for avelumab + BSC vs BSC alone across subgroups. No significant treatment-by-cycle interaction (at 0.05 level) was observed. Conclusions: Improved OS was observed with avelumab 1L maintenance vs BSC alone irrespective of duration or cycles of 1L chemotherapy received prior to entering the trial. Among patients who stopped 1L chemotherapy prior to 6 cycles, avelumab 1L maintenance still provided an OS benefit. Clinical trial information: NCT02603432 . Research Sponsor: Pfizer Inc, Pharmaceutical/Biotech Company[Table: see text]

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Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

Cancers ◽

10.3390/cancers13225629 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5629

Author(s):

Yusuke Sugino ◽

Takeshi Sasaki ◽

Manabu Kato ◽

Satoru Masui ◽

Kouhei Nishikawa ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Psoas Muscle ◽

Hounsfield Unit ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cross Sectional

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm2) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC.

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Impact of genomic aberrations and additional therapies on survival outcomes of patients with operable non-small cell lung cancer (NSCLC) from the NEOSTAR study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8542 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8542-8542

Author(s):

Nicolas Zhou ◽

Boris Sepesi ◽

Cheuk Hong Leung ◽

Heather Y. Lin ◽

William Nassib William ◽

...

Keyword(s):

Lung Cancer ◽

Median Time ◽

Proportional Hazards Model ◽

Primary Lung Cancer ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Egfr Mutations ◽

Genomic Aberration ◽

Curative Intent ◽

Genomic Aberrations

8542 Background: The NEOSTAR study compared nivolumab (N) vs. nivolumab plus ipilimumab (NI) with major pathological response (MPR; ≤10% viable tumor) as primary outcome. We report updated rates of treatment failure (TF), including in patients whose tumors harbored genomic aberrations, and outcomes of additional treatments. Methods: Patients (pts) with stage I-IIIA resectable NSCLC (AJCC 7th) were randomized to either neoadjuvant N or NI followed by surgery (n = 44). TF was defined as radiographic and/or biopsy-proven recurrence from primary lung cancer and/or death (treatment or cancer-related). Additional systemic therapy at recurrence included immuno-oncology (IO)-based therapy (IO or chemo-IO), targeted therapy (TT), or chemotherapy. Disease control rate (DCR) was defined as the proportion of pts with radiographic objective responses and stable disease at first restaging. Cox proportional hazards model was used to associate baseline characteristics and time to TF. Results: A total of 44 randomized pts were evaluated, the median follow-up was 35 months (mts) as of February 4, 2021. Among the 12 TF pts (12/44, 27%), 42% (5/12) did not undergo surgery on trial, 9 (9/44, 20%) experienced recurrence and 6 (6/44, 14%) died (1 non-cancer-related, 5 cancer-related). TF was less likely in smokers vs. never smokers (hazard ratio = 0.20, 95% confidence interval = 0.06-0.65, p = 0.007). Among pts with pathological specimen resected on trial, MPR was achieved in 40% (12/30) of non-TF pts. Only 1 (1/7, 14%) TF pt achieved MPR, but died of a non-cancer related cause. TF-free survival rate at 2 years was 92% in MPR and 78% in non-MPR pts. Eight (8/9, 89%) pts had tumors with canonical oncodriver aberrations (5 EGFR mutations, 1 with STK11+ KRAS Q61H mutations, 1 ALK translocation and 1 RET fusions). Of the 9 recurrences, 44% (4/9) were treated with IO therapy, and all 7 pts with targetable aberrations were treated with TT (3 after retreatment with IO therapies). Of the 4 pts retreated with IO therapy, duration between end of neoadjuvant and retreatment were 20, 17, 23, and 19 mts. Duration from retreatment until progression (PD) were 1, 1, and 2 mts, respectively. Last pt was treated without PD for 2 mts but switched to TT due to discovery of genomic aberration. IO retreatment achieved 25% DCR (1/4). In comparison, the DCR for TT treated pts was 71% (5/7, p = 0.242). Median time to treatment was 21 mts, and median time to PD was not reached. Among 32 non-TF pts, 12 had genomic analysis and 7 aberrations were found in 6 pts (2 STK11, 2 ERBB2, 1 STK11 + 1 KRAS G12C, and 1 KRAS G12C mutation). Conclusions: A 27% TF rate was observed after neoadjuvant IO. TF was less likely to occur in smokers and MPR pts, and 42% of TF pts did not undergo curative-intent surgery on trial. Genomic aberrations were common in pts with recurrence (89%), and treatment with TT achieved 71% DCR vs. 25% DCR with IO-based retreatment. Clinical trial information: NCT: 03158129.

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The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma

Urologia Internationalis ◽

10.1159/000511650 ◽

2020 ◽

pp. 1-7

Author(s):

Volkan İzol ◽

Mutlu Deger ◽

Ender Ozden ◽

Deniz Bolat ◽

Burak Argun ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Upper Urinary Tract ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Recurrence Time ◽

Tumor Biopsy ◽

Group 2 ◽

Group 1

Objective: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. Results: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Conclusion: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.

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Frequency of use and outcome of surgical resection in the management of malignant mesothelioma in a community-based population: Results in 5,937 patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7510 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7510-7510

Author(s):

R. M. Flores ◽

E. Riedel ◽

J. S. Donington ◽

L. Krug ◽

K. Rosenzweig ◽

...

Keyword(s):

Surgical Resection ◽

Median Survival ◽

Malignant Pleural Mesothelioma ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Univariate Analysis ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Pleural Mesothelioma ◽

Tertiary Referral

7510 Background: Multimodality therapy of mesothelioma patients treated at specialized tertiary hospitals report surgical resection rates of 42% (Flores RM et al. Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center. J Thorac Oncol 2007;2(10):957–965.). Treatment strategies in the community are less well defined and surgical expertise is not readily available. We undertook this study to evaluate the rate of surgical resection and its association with survival in a non-tertiary based population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched from 1990 - 2004. Variables analyzed included age, sex, race, year of diagnosis, laterality, vital status, stage, surgery, and reasons for no surgery. The association of resection on overall survival was estimated by the Kaplan-Meier method and examined in a Cox proportional hazards model adjusting for covariates. Results: Pathologically proven malignant pleural mesothelioma was identified in 5,937 patients: 1,166 women, 4,771 men; median age was 70 years. Surgical resection rate was 11% (n=636). Univariate analysis demonstrated a median survival of 13 months with surgical resection and a median survival of 7 months in the non-resected group (p<0.0001). Multivariate analysis demonstrated improved survival for surgically resected patients (HR 0.7, p<0.0001), controlling for age, gender, and stage. Conclusions: Surgical resection was associated with improved survival when controlling for age, stage, and gender. However, the rate of surgical resection was much lower in the community when compared to tertiary referral centers. Treatment efforts should be focused on a multidisciplinary approach which includes surgical evaluation. No significant financial relationships to disclose.

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Denosumab and zoledronic acid treatment in patients with genitourinary cancers and bone metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5079 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5079-5079 ◽

Cited By ~ 2

Author(s):

Luis Costa ◽

Karim Fizazi ◽

Fred Saad ◽

Janet Elizabeth Brown ◽

Roger Von Moos ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Disease ◽

Proportional Hazards Model ◽

Transitional Cell ◽

Cox Proportional Hazards ◽

Metastatic Bone Disease ◽

Cox Proportional Hazards Model ◽

Phase Iii ◽

Pivotal Phase ◽

Significant Difference

5079 Background: Phase III trial results showed that denosumab is superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) in patients with cancer and metastatic bone disease (Lipton et al; 2012, Eur J Cancer). Genitourinary (GU) cancers are some of the most commonly diagnosed cancers worldwide. We now compare the efficacy and safety of denosumab (DMAb) or ZA in a subgroup analysis of patients with GU cancers enrolled in the pivotal phase III trials. Methods: Patients were randomized 1:1 to receive DMAb (120 mg, SC) or ZA (4 mg, IV, adjusted for renal function) every 4 weeks. Daily calcium and vitamin D supplements were strongly recommended. Time to 1st on-study SRE, using a Cox proportional hazards model, time to 1st and subsequent on-study SRE, using the Anderson-Gill model, and safety were evaluated for the GU subgroup in an ad hoc analysis. Results: 2,128 patients (1,052 DMAb; 1,076 ZA) had GU cancers (prostate = 1,901, renal = 155, bladder = 63, and transitional cell = 9). DMAb significantly delayed the time to 1st on-study SRE by 4.0 months compared with ZA (20.7 months vs 16.7 months) in patients with GU cancers (Table). DMAb also significantly delayed the time to 1st and subsequent on-study SRE. Time to disease progression and overall survival were similar between treatment groups. Adverse events (AEs) and serious AEs were reported by similar percentages of patients in both groups (AEs: 96.9% denosumab, 96.8% ZA; serious AEs: 62.8% denosumab, 60.2% ZA). 14.6% of DMAb pts and 15.9% of ZA pts had a renal AE. Hypocalcemia was reported for 12.9% of DMAb patients and 6.2% of ZA patients. There was no significant difference in the incidence of positively adjudicated osteonecrosis of the jaw between the DMAb (2.2%) and ZA (1.6%) groups (p=0.34). Conclusions: Among patients with GU cancers and metastatic bone disease, DMAb was superior to ZA in preventing SREs. Clinical trial information: NCT00330759 and NCT00321620. [Table: see text]

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Sequential treatment of advanced or metastatic renal cell carcinoma (mRCC): What is effective? Data from the German RCC registry.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.499 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 499-499

Author(s):

Lothar Mueller ◽

Peter J. Goebell ◽

A. Lueck ◽

Friedrich Overkamp ◽

Michele Vogt ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Negative Impact ◽

Positive Impact ◽

Current Treatment ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Sequential Treatment ◽

Line Therapy ◽

Systemic Treatments

499 Background: In addition to Bevacizumab+Interferon, current treatment options of mRCC imply two major intracellular modes of action and thus classes of therapies: the four approved tyrosine kinase inhibitors (TKI) Sunitinib, Sorafenib, Pazopanib, Axitinib and the two inhibitors of the mammalian target of rapamycin (mTOR) Temsirolimus, Everolimus (EVE). With their availability efficacy of sequential treatment has become a central question of clinical research. While clinical trials recruit highly selected patients (pts) and usually focus on a single line of therapy, collected data of clinical registries may represent all patients and all sequential therapies. Methods: Starting in 12/2007 the registry aims to enrol a total of 1500 patients from more than 120 oncology and urology outpatient centres collecting data on all systemic treatments, outcome, patient and tumour characteristics. Here, the effectiveness of two 1st – 2nd-line sequential treatments, TKI–TKI vs TKI–EVE, was investigated with a multivariate cox proportional hazards model considering potential confounding variables (age, comorbidity, body mass index (BMI), duration of 1st-line therapy, Motzer’s score and type of sequential treatment). Results: At the time of analysis, 481 pts had received sequential 1st- and 2nd-line treatment between 2007 and 2012. In total, 70% of pts received 1st-line TKI-treatment. 46% of these pts received the sequential treatment TKI–TKI, 25% received TKI–EVE. In the multivariate analysis, high BMI (HR 0.946, 95% CI 0.9018-0.9923, p<.05) and a long duration of 1st-line-therapy (HR 0.9967, 95% CI 0.9956-0.9979, p<.001) had a significant positive impact on OS, whereas high risk Motzer`s score (HR 8.9992, 95% CI 2.4231-33.4228, p<.01) had a significant negative impact on OS. However, the type of sequential treatment had no impact on OS (HR 1.0658, 95% CI0.6463-1.7576, p=0.802). Conclusions: The RCC Registry provides an overview of the current treatment reality in routine medical practice. TKI are the most frequently applied 1st-line treatments, followed by TKI or mTOR inhibitors. Our data show no difference concerning the effectiveness of the sequential treatment TKI–TKI vs TKI–EVE.

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Phase III randomized study of vinorelbine (V), gemcitabine (G) followed by docetaxel (D) (VGD) versus paclitaxel (P) and carboplatin (C) (PC) in patients (pts) with advanced non-small cell lung cancer (NSCLC) (Japan Multinational Trial Organization LC00–03)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7013 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7013-7013

Author(s):

M. Kawahara ◽

M. Ogawara ◽

Y. Nishiwaki ◽

K. Kubota ◽

K. Komuta ◽

...

Keyword(s):

Lung Cancer ◽

Advanced Nsclc ◽

Randomized Study ◽

Stage Iv ◽

Progression Free Survival ◽

Stage Iiib ◽

Phase Iii ◽

Grade 3 ◽

Level Of Significance ◽

Ecog Ps

7013 Background: Our phase II study of non-platinum VGD for advanced NSCLC demonstrated excellent results with the median survival time (MST) of 15.7 mos and a 1-year survival rate of 59% (Brit J Cancer 88:42,2003). A phase III trial was performed to determine the survival benefit of VGD compared with PC for advanced NSCLC as a Japan-SWOG Lung Cancer Common Arm Trial. Methods: Between Mar 2001 and Apr 2005, 401 chemo-naïve NSCLC pts with Stage IIIB with pleural effusion or Stage IV without brain metastasis, who had ECOG PS 0–1, were randomized to VGD; V 25 mg/m2 iv and G 1000 mg/m2 iv, days 1, 8, every 21 days for 3 cycles followed by D 60 mg/m2 iv, d1, every 21 days for 3 cycles or PC; C AUC=6 iv and P 225 mg/m2 iv, day 1, every 21 days for 6 cycles. The primary endpoint was overall survival (OS). For a two-sided test at the 5% level of significance and power of 85%, the number of pts required to detect a 40% difference in MST was 400. Results: 393 pts (196 VGD, 197 PC) were evaluable for response, OS and toxicity. Baseline demographics were balanced (VGD vs PC): median age 65 yrs(both arms);male(74 vs 69%); PS 0 40%(both arms);Stage IIIB (17 vs 18%); Ad/Sq (66%/23% vs 76%/15%). There were 238 deaths with a median follow-up of 23 mos. 49% in VGD and 29% in PC arm completed 6 cycles (p=0.00005). Response rates in arms VGD/PC were 23% vs 36% (p= 0.008). There were no significant differences in progression free survival, OS, 1- and 2-yr survivals between VGD and PC arms: 5.9 vs 6.0 mos (p=0.95, Log rank), 13.1 vs 13.8 mos (MST, p=0.28, Log rank), 55.6 vs 55.5%, and 27.6 vs 31.8%. Grade 3/4 toxicities in arms VGD/PC were: neutropenia (G4) (30 vs 54%, p<0.00001), thrombocytopenia (4 vs 6%), febrile neutropenia (20 vs 19%), neuropathy (2 vs 21%, p<0.00001), pulmonary (9 vs 2%, p=0.0006). There were 2 treatment-related deaths (pneumonitis) in VGD arm. Conclusions: Non-platinum triplet chemotherapy had comparable activity in pts with advanced NSCLC. The VGD had significantly less myelosuppression, but more pulmonary toxicity than PC. No significant financial relationships to disclose.

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