First-line PD1/PD-L1 inhibitors for platinum-ineligible advanced urothelial carcinoma (UC).

432 Background: FDA modified the label for the use of 1st-line pembrolizumab or atezolizumab therapy to PD-L1 high cisplatin-ineligible or platinum-ineligible UC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD1/PD-L1 inhibitors for platinum-ineligible pts are unclear. We conducted a retrospective study to evaluate clinical outcomes with first-line PD1/PD-L1 inhibitors for platinum-ineligible pts with advanced UC in a real-world setting. Methods: We collected data retrospectively from 6 institutions. The following criteria were deemed to render pts platinum-ineligible although physician discretion was also allowed: Cr Cl < 30 ml/min, ECOG-PS 3, Both Cr Cl 30 to < 60 AND ECOG-PS 2. Demographic and clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was done to study the association of baseline variables with response and survival. Results: Data were available for 45 pts. Pts received atezolizumab [n = 24], pembrolizumab [n = 11], nivolumab [n = 7] and durvalumab [n = 3]. The mean age was 72.2 (range 45-90) years. The reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 17), ECOG-PS 3 (n = 3), ECOG-PS 2 plus Cr Cl < 60 ml/min (n = 7), elderly with co-morbidities (n = 12), and reason was unavailable for 6 pts. The median OS was 37 weeks (CI 30-80). ORR was 27.3%: Complete response in 3 pts [6.8%], partial response in 9 pts [20.5%], stable disease in 11 pts [25%] and progressive disease in 21 pts [47.7%] and data for 1 patient was unavailable. Toxicity of any grade were seen in 42.2% of pts and Grade ≥3 toxicity in 9 pts’ [20%]. There were no treatment-related deaths. Anemia (HR = 0.75, 95% CI 0.62 - 0.92, P = 0.005) and liver metastasis (HR = 1.17, 95% CI 0.47 - 2.93, P = 0.017) correlated with shorter OS. Conclusions: To our knowledge, this is the 1st report of efficacy and toxicity of PD1/PD-L1 inhibitors as1st-line therapy for platinum ineligible UC. Data appear comparable to those reported previously in unselected cisplatin-ineligible pts receiving pembrolizumab or atezolizumab in phase II trials. Validation is needed in larger datasets and prospective trials.

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First-line PD(L)1 inhibitors for platinum-ineligible advanced urothelial carcinoma (aUC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16024 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16024-e16024

Author(s):

Archana Agarwal ◽

Gregory Russell Pond ◽

Ruby Gupta ◽

Moshe Chaim Ornstein ◽

Pedro C. Barata ◽

...

Keyword(s):

Cox Regression ◽

Locally Advanced ◽

Complete Response ◽

Cox Regression Analysis ◽

Best Response ◽

Advanced Urothelial Carcinoma ◽

Grade 3 ◽

Using Data ◽

Line Setting ◽

Ecog Ps

e16024 Background: FDA modified the label for 1st-line pembrolizumab or atezolizumab to PD-L1 high cisplatin-ineligible or platinum-ineligible aUC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD-(L)1 inhibitors for platinum-ineligible pts are unclear. We hypothesized that treatment response and outcomes are comparable to data reported in trials in the 1st line setting of aUC, and conducted a retrospective study to test this hypothesis using data outside the clinical trial setting. Methods: We collected data from 8 institutions for aUC pts with locally advanced unresectable or metastatic UC. The following criteria were used to define pts platinum-ineligible while comorbidities, age and physician discretion were also allowed: Cr Cl < 30 ml/min, ECOG PS 3, Cr Cl 30-59 ml/min and ECOG PS 2. Demographic & clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was used to explore associations of baseline variables with response and outcomes. Results: Data were available for 79 pts. Pts received atezolizumab [n = 41], pembrolizumab [n = 28], nivolumab [n = 7] or durvalumab [n = 3]. Median age was 74 years (45-93). Reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 26), ECOG PS 3 (n = 8), ECOG-PS 2 and Cr Cl < 30-59ml/min (n = 14), elderly/co-morbidities (n = 17), and ‘unavailable’ (n = 14). Median OS was 45 weeks (CI 32-80) and ORR was 27.9%: Complete response in 4 pts [5.1%], partial response in 18 pts [22.8%], stable disease in 19 pts [24.1%], progressive disease in 34 pts [43 %]; data for 4 pts [5.1%] was unavailable for best response. Toxicity of any grade and Grade ≥3 was seen in 41.8% and 31.7% of pts, respectively. Hemoglobin (HR = 0.78, 95% CI 0.68 - 0.90, P = 0.001) and liver metastasis (HR = 1.13, 95% CI 0.51 - 2.53, P = 0.036) correlated with OS. Conclusions: The efficacy and toxicities of 1st-line PD-(L)1 inhibitors for platinum-ineligible pts outside clinical trials appear comparable to those reported in trials for unselected cisplatin-ineligible pts. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible pts with aUC warrant evaluation of novel safe and effective agents.

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Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Neuro-Oncology Practice ◽

10.1093/nop/npac004 ◽

2022 ◽

Author(s):

Nayan Lamba ◽

Malia McAvoy ◽

Vasileios K Kavouridis ◽

Timothy R Smith ◽

Mehdi Touat ◽

...

Keyword(s):

Cox Regression ◽

Extent Of Resection ◽

First Line ◽

Short Term ◽

Who Grade ◽

Cox Regression Analysis ◽

Significant Difference ◽

Pcv Chemotherapy ◽

Grade 3 ◽

National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

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Preliminary results for the combination of docetaxel, oxaliplatin and capecitabine as a first-line treatment for metastatic oesophagogastric cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14076 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14076-14076

Author(s):

S. Viteri ◽

J. Rodríguez ◽

M. González Cao ◽

J. De La Cámara ◽

A. Chopitea ◽

...

Keyword(s):

Performance Status ◽

Median Number ◽

New Drugs ◽

Phase Ii Trials ◽

First Line ◽

Ecog Performance Status ◽

Standard Regimen ◽

Grade 3 ◽

Metastatic Sites ◽

Ecog Ps

14076 Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m2 day 1, O 85 mg/m2 day 1 and oral C 650mg/m2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile No significant financial relationships to disclose.

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Decitabine As First Line Treatment in Acute Myeloid Leukemia of the Elderly: Real-Life Experience from a Single Center

Blood ◽

10.1182/blood-2019-123028 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5137-5137

Author(s):

Eleni Bouronikou ◽

Eleni Georgiadi ◽

George Vassilopoulos

Keyword(s):

Myeloid Leukemia ◽

Cox Regression ◽

Real Life ◽

The Elderly ◽

Hematological Toxicity ◽

First Line ◽

Cox Regression Analysis ◽

Real Life Setting ◽

Duration Of Response ◽

The Mean

Background: Acute myeloid leukemia, a disease common in the elderly, remains a therapeutic challenge for the hematologist. Patients are compromised and have comorbidities that make the treatment-related toxicities, difficult to manage; the net effect is treatment discontinuation. Therefore, hypomethylating agents present a reasonable and manageable therapeutic approach; our study provides information on the real-world data of such an approach in a cohort of patients. Patients and methods: A total of 44 patients were enrolled in the present study. They were referred to our hospital between January 2016 and March 2018. These patients were suffering from AML and they received decitabine as first line treatment (if they were not eligible for intensive chemotherapy) or as salvage treatment. The primary objective was to evaluate the efficacy and safety of decitabine in real life setting. The drug was administered at a dose of 20 mg/m2 body surface area by intravenous infusion over 1 hour, repeated daily for 5 consecutive days. Results: All patients received treatment with decitabine. The median age at diagnosis was 71.8 years ranging from 48 to 83 years old. The mean decitabine cycles were 2.6. Out of the 44 patients only 25% received ≥ 4 cycles of the drug while 20 patients received only 1 decitabine course. The Overall Response Rate (ORR=CR+PR) was 13.7%. CR was achieved in 1/44 patient (2.3 %). PR was achieved in 5/44 patients (11.4%) while SD was observed in 8/44 patients (18.2%). For the patient achieved CR, the duration of response was 9 months, while the median duration of response in the group of patients with PR and SD was 7 months and 4.5 months respectively. All patients experienced adverse events with hematological toxicity being the most common, following by infections. Thrombocytopenia was the most common among hematological toxicity (82.5%), while anemia and neutropenia were recorded in 45% and 55% of the cases respectively. The main cause of treatment discontinuation was the progression of the disease. The mean survival time was 6.8 months. Results from univariate Cox regression analysis for survival showed a significant association with comorbidities and number of cycles of decitabine. When multiple Cox regression analysis in a stepwise method was conducted it was found that patients with comorbidities had 2.5x greater hazard as compared to those without comorbidities. Additionally, patients treated with more than one cycles of decitabine had 71% lower hazard as compared to those treated with only one cycle. Conclusion: These data from a single center experience provide information about the efficacy and safety profile of decitabine in real life setting. Although the number of the patients is low, however our analysis confirms the acceptable use of decitabine in AML as first line or as salvage treatment especially in compromised patients. Decitabine is a well-tolerated drug with adverse events consistent with the safety profile of the drug and it appears as a reasonable treatment for patients with comorbidities such as the elderly or for the heavily treated. Disclosures No relevant conflicts of interest to declare.

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Phase III study of standard triweekly versus dose-dense biweekly capecitabine (C) + oxaliplatin (O) + bevacizumab (B) as first-line treatment for metastatic colorectal cancer (mCRC): XELOX-A-DVS (dense versus standard): Interim analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4078 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4078-4078

Author(s):

H. Hurwitz ◽

Y. Z. Patt ◽

D. Henry ◽

L. Garbo ◽

E. P. Mitchell ◽

...

Keyword(s):

Cox Regression ◽

Objective Response ◽

Hazard Ratio ◽

Statistical Testing ◽

Phase Iii ◽

First Line ◽

Open Label ◽

Cox Regression Analysis ◽

Grade 3 ◽

Dose Dense

4078 Background: Every 3 week (Q3W) COB has been shown to be highly active and non-inferior to FOLFOX+B in first-line mCRC. Phase II data suggest that dose-dense every 2 week (Q2W) COB may be significantly more active and better tolerated than Q3W COB. Methods: XELOXA-DVS was a phase III, open-label study of 435 patients with chemonaive mCRC who met standard eligibility criteria. Patients were randomized to Q3W: C 850 mg/m2 BID d1–14 + O 130 mg/m2 d1 + B 7.5 mg/kg d1 or Q2W: C 1500 mg/m2 BID d1–7 + O 85 mg/m2 d1 + B 5 mg/kg d1 for up to 72 weeks. Complete surgical resection was allowed using pre-defined criteria. The primary endpoint, progression-free survival (PFS), was estimated using the Kaplan- Meier method, while the hazard ratio and 95% CI were estimated using Cox regression analysis, based on the intent-to-treat population. No formal statistical testing was conducted. Results: The median PFS was 8.4 months (Q2W) and 9.7 months (Q3W) (hazard ratio [HR]=0.84; 95% CI=0.62–1.13). The median PFS (on-treatment) was 9.1 months and 10.2 months, respectively (HR=0.81). Of the 72 and 73 patients with disease progression (DP), the median time to DP was 9.4 and 10.8 months, respectively (HR=0.86). The objective response rates were 21.7% vs 29.4%, respectively (HR=1.05). Patients in the Q2W vs Q3W group experienced higher rates of grade 3/4 diarrhea (29% vs 24%), hand-foot syndrome (12% vs 8%), and treatment discontinuation rates (40% vs 20%), respectively. Other grade 3/4 toxicities (>5%, Q2W vs Q3W) included fatigue (13% vs 13%), dehydration (12% vs 10%), nausea (8% vs 9%), peripheral neuropathy (5% vs 9%), anorexia (5% vs 7%), and abdominal pain (5% vs 7%). Conclusions: At the dose and schedule used, dose-dense Q2W COB was not superior to standard Q3W COB. These data further confirm the activity and tolerability of Q3W COB. The activity and tolerability of a lower C dose Q2W, with more aggressive dose reduction, combined with B and O or irinotecan is currently being evaluated (X-BIO). [Table: see text]

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Efficacy and safety of cetuximab, oxaliplatin, and capecitabine as first-line therapy for metastatic colorectal cancer (mCRC): Results of a phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15013 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15013-e15013

Author(s):

S. A. Barroso ◽

E. Sanches ◽

M. Ferreira ◽

M. Passos ◽

A. Sá ◽

...

Keyword(s):

Complete Response ◽

Efficacy And Safety ◽

First Line ◽

Open Label ◽

Maximum Width ◽

Overall Response ◽

First Line Therapy ◽

Highly Active ◽

Grade 3 ◽

Ecog Ps

e15013 Background: To date, few studies have investigated the use of cetuximab in combination with oxaliplatin and capecitabine in the first-line treatment of mCRC. We therefore conducted an uncontrolled, open-label, multicenter study to evaluate the efficacy and safety of this combination in this setting. Methods: Patients (pts) received intravenous (iv) oxaliplatin 130 mg/m2 (3h day 1) plus capecitabine 1,000 mg/m2 twice daily (days 1–14) every 3 weeks (XELOX) and cetuximab 400 mg/m2 iv week 1 then 250 mg/m2 weekly over 8 cycles. Treatment was continued until disease progression (PD), unacceptable toxicity or completion of therapy. Pts were followed until death. The primary endpoint was overall response rate (ORR). A sample size of 45 pts was necessary to obtain a 95% confidence interval (CI) for ORR with a maximum width of 15% assuming an ORR of 50–80%. Results: From Sept 2005-Jan 2007, 49 pts were enrolled (ITT population): 67% male, mean age 60 (range: 44–75) years, 56.3% ECOG PS 0. Of 42 pts evaluable for ORR, 4 (9.5%) achieved a complete response, 31 (73.8%) a partial response, 6 (14.3%) had stable disease and 1 (2.4%) had PD. The ORR was 83.3% (95% CI: 72.0–94.6%). Median time to progression was 9 months (95% CI: 7.1–10.9 months). Of the 49 pts evaluable for safety, 27 (55.1%) had at least one grade 3/4 toxicity, 42 (85.7%) had acne-like rash (8 pts [16.3%] grade 3). Most common grade 3/4 toxicities included diarrhea (n=9;18.4%) and changes in potassium (n=6;12.2%). 24 (3.4%) AEs led to dose reductions (12 unrelated, 10 unlikely and 2 definitely related to cetuximab), 56 (7.8%) led to a dose delay (12 unrelated, 28 unlikely, 8 possibly, 6 probably, 2 definitely related to cetuximab) and 2 (0.3%) led to infusion rate reduction (not treatment related). 27 (55.1%) pts discontinued therapy: 10 (20.4%) due to AEs, 7 (14.3%) PD, 10 (20.4%) other reasons. 33 (67.3%) pts died: 30 (61.2%) due to PD, 2 (4.1%) intercurrent event/disease, 1 (2.0%) acute pancreatitis. The results according with the HGFR evaluation by IHC will be presented. Conclusions: In this first-line mCRC study, 83.3% of pts treated with cetuximab, oxaliplatin and capecitabine achieved an overall response. This combination appears to be a highly active and well-tolerated regimen. No significant financial relationships to disclose.

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Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma (UC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.308 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 308-308

Author(s):

Neeraj Agarwal ◽

Kenneth M. Boucher ◽

Benjamin Maughan ◽

Syed A. Hussain ◽

Donald S. Kaufman ◽

...

Keyword(s):

Phase Ii ◽

Randomized Trials ◽

Pooled Analysis ◽

Phase Ii Trials ◽

First Line ◽

Split Dose ◽

First Line Therapy ◽

Random Variability ◽

Advanced Urothelial Carcinoma ◽

Grade 3

308 Background: Weekly gemcitabine with day 1 cisplatin 70 mg/m2 every 3-4 weeks (GC) is considered a conventional first line chemotherapy for advanced UC. Weekly split-dose cisplatin (delivering a similar cumulative dose per cycle) with concurrent weekly gemcitabine (wGC) may be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety. Methods: Two trials of wGC (n=74) patients and 3 trials of GC (n=131) were identified. A Cr Cl ≥60 ml/minute was required, except one trial of wGC that enrolled 19 patients with Cr Cl 40-60 ml/minute. Since the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), which allows for heterogeneity between studies in the same grouping, for response rates and grade ≥3 toxicities were calculated. Long-term outcomes were not uniformly reported and hence inevaluable. Results: The 95% CI overlapped, suggesting agreement between wGC and GC (Table). After accounting for random variability, no clear difference in the CR, PR, SD and grade ≥3 toxicities between GC and wGC were observed. Limitations of a retrospective study apply. Conclusions: GC and wGC yielded similar responses and grade ≥3 toxicities in advanced UC. These results are hypothesis-generating and in the absence of randomized trials, wGC should not be routinely substituted for GC in cisplatin-eligible patients. [Table: see text]

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First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

Scientific Reports ◽

10.1038/s41598-021-81025-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kiyoharu Fukushima ◽

Seigo Kitada ◽

Sho Komukai ◽

Tomoki Kuge ◽

Takanori Matsuki ◽

...

Keyword(s):

Pulmonary Disease ◽

Mycobacterium Avium ◽

Propensity Scores ◽

Cox Regression ◽

Line Treatment ◽

First Line ◽

Standard Regimen ◽

Cox Regression Analysis ◽

First Line Treatment

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.

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The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen

Technology in Cancer Research & Treatment ◽

10.1177/15330338211019433 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110194

Author(s):

Nan Geng ◽

Jingwei Su ◽

Zhikun Liu ◽

Cuimin Ding ◽

Shaonan Xie ◽

...

Keyword(s):

Genetic Variation ◽

Regression Analysis ◽

Mrna Expression ◽

Advanced Nsclc ◽

Cox Regression ◽

Chemotherapy Regimen ◽

Efficacy And Safety ◽

First Line ◽

Cox Regression Analysis ◽

Tissue Specimens

Objective: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA). Kinase insert domain receptor (KDR) is the most important target of VEGFA. The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. Results: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium ( P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% ( P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively ( P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively ( P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens ( P < 0.001). Conclusion: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR.

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Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11565 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11565-11565

Author(s):

Scott Schuetze ◽

Michael Rothe ◽

Pam K. Mangat ◽

Liz Garrett-Mayer ◽

Funda Meric-Bernstam ◽

...

Keyword(s):

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

Stage Design ◽

Secondary Endpoints ◽

Grade 3 ◽

Ecog Ps ◽

Stage 1 ◽

Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

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