The impact of prior chemotherapy (PrC) on immunotherapy outcomes in non-small cell lung cancer (NSCLC) patients: Real data from a mono-institutional study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21639-e21639
Author(s):  
Marianna Macerelli ◽  
Simona Rizzato ◽  
Marco Giavarra ◽  
Francesca Valent ◽  
Monica Cattaneo ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Real Data ◽  
Tumor Burden ◽  
Interquartile Range ◽  
Best Response ◽  
Before And After ◽  
Ecog Ps ◽  
Nsclc Patients ◽  
The Impact

e21639 Background: Immunotherapy has changed the paradigm on NSCLC treatment. No widespread and reproducible predictive biomarkers have been established. We analyzed how PrC could affect ICI outcomes. Methods: We conducted a retrospective observational study and analyzed all NSCLC patients (pts) treated with ICI (nivolumab or atezolizumab or pembrolizumab) in our institution from 2015 to 2018 and followed until January 2020. All pts had received at least one PrC. We recorded clinical features of pts both before and after ICI treatment. Results: A total of 83 pts were included, with a median age of 69 (range, 47-82). Sixty pts (73%) were male, 74 (89%) were smokers and 81 (97%) had ECOG PS 0-1. Thirteen (15.7%) pts had a immune-related toxicity (iRT, G1-G2 76.9% and G3-G4 23.1%) and 21 (25.3%) continued ICI therapy beyond progression disease (PD). Patients with a PD as best response to PrC had more probability to reach a PD with ICI (p = 0.06). Median Progression-Free Survival (PFS) on ICI was 2.9 months (interquartile range, 1.9-9.4) with no statistical difference between pts with oligo- or diffuse progression (≤ or > 5 metastasis) during PrC (p = 0.42). Corticosteroids use was associated with worse PFS (p < 0.01). Median Overall Survival (OS) was 9.1 months (interquartile range, 3.3-26.5), with a benefit for pts with a stable disease (SD) or partial response (PR) to PrC (p = 0.02), for pts who experimented iRT (p = 0.04) and who didn’t receive corticosteroids (p < 0.01). In multivariate analysis liver or brain metastases (HR 8.8, 95% CI 2.9-26.8 and HR 2.2, 95% CI 0.6-8.1), coticosteroids use (HR 3.7, 95% CI 1.3-10.5) or previous cisplatin-based chemotherapy (HR 8.4, 95% CI 2.3-30.1) were associated with worse OS. Instead, pts whit iRT (HR 0.4, 95% CI 0.1-1.3) and PR as best response to PrC (HR 0.8, 95% CI 0.3-2.0) had a better OS. Conclusions: Our study confirms literature data and suggests that PrC could affect ICI outcomes. Tumor burden seems not to influence ICI outcomes, unlike response rate to PrC. Systemic corticosteroids use and iRT predicts ICI outcomes.

scholarly journals The role of opioids in cancer response to immunotherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Andrea Botticelli ◽  
Alessio Cirillo ◽  
Giulia Pomati ◽  
Bruna Cerbelli ◽  
Simone Scagnoli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Immune System ◽  
Progression Free Survival ◽  
Concomitant Administration ◽  
Tumor Burden ◽  
Cox Proportional Hazard ◽  
Immunomodulatory Action ◽  
Immune System Modulation ◽  
Ecog Ps ◽  
The Impact

Abstract Background The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities. Methods This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival. Results One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37–2.09, p < 0.0001; median OS, 4 months vs. 35 months, HR 1.60, 95% CI 1.26–2.02, p < 0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥ 1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden. Discussion Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well. Conclusions A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.

scholarly journals The Role of Opioids in Cancer Response to Immunotherapy

2021 ◽  
Author(s):  
Andrea Botticelli ◽  
Alessio Cirillo ◽  
Giulia Pomati ◽  
Bruna Cerbelli ◽  
Simone Scagnoli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Immune System ◽  
Progression Free Survival ◽  
Concomitant Administration ◽  
Tumor Burden ◽  
Cox Proportional Hazard ◽  
Immunomodulatory Action ◽  
Immune System Modulation ◽  
Ecog Ps ◽  
The Impact

Abstract Background: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities.Methods: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival. Results: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37-2.09, p<0.0001; median OS, 4 months vs. 35months, HR 1.60, 95 % CI 1.26-2.02, p <0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden.Discussion: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well. Conclusions: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.

scholarly journals Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tereza Vaclova ◽  
Ursula Grazini ◽  
Lewis Ward ◽  
Daniel O’Neill ◽  
Aleksandra Markovets ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr T790m

AbstractAdvanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the EGFR T790M-positive clone impacts response to osimertinib. T790M subclonality, as assessed by a retrospective NGS analysis of 289 baseline plasma ctDNA samples from T790M‐positive advanced NSCLC patients from the AURA3 phase III trial, is associated with shorter progression-free survival (PFS), both in the osimertinib and the chemotherapy-treated patients. Both baseline and longitudinal ctDNA profiling indicate that the T790M subclonal tumours are enriched for PIK3CA alterations, which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by PI3K pathway inhibitors. Overall, our results elucidate the impact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could help define appropriate combination therapies in these patients.

Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9533-9533
Author(s):  
Ines Pires Da Silva ◽  
Judith M. Versluis ◽  
Tasnia Ahmed ◽  
Douglas Buckner Johnson ◽  
Jennifer Soon ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Initial Response ◽  
Best Supportive Care ◽  
First Line ◽  
Disease Characteristics ◽  
Best Response ◽  
Investigational Drugs ◽  
Ecog Ps

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]

Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma

2021 ◽  
Author(s):  
Alice Boileve ◽  
Elise Mathy ◽  
Charles Roux ◽  
Matthieu Faron ◽  
Julien Hadoux ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Burden ◽  
Interquartile Range ◽  
First Line ◽  
Chemotherapy Administration ◽  
Metastatic Sites

Abstract Purpose European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients. Methods A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. Results Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group. Conclusion Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and &lt;VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P &lt; .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

scholarly journals Prospective Evaluation of the Strategy of Functionally Optimized Coronary Intervention

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Barry F. Uretsky ◽  
Shiv K Agarwal ◽  
Srikanth Vallurupalli ◽  
Malek Al‐Hawwas ◽  
Rimsha Hasan ◽  
...  
Keyword(s):  
Coronary Intervention ◽  
Interquartile Range ◽  
Fractional Flow ◽  
Long Term Outcomes ◽  
Flow Reserve ◽  
Pressure Wire ◽  
Percutaneous Coronary ◽  
Before And After ◽  
The Impact

Background Long‐term outcomes after percutaneous coronary intervention (PCI) relate in part to residual ischemia in the treated vessel, as reflected by post‐PCI fractional flow reserve (FFR). The strategy of FFR after PCI and treatment of residual ischemia—known as functionally optimized coronary intervention (FCI)—may be feasible and capable of improving outcomes. Methods and Results Feasibility and results of FCI using an optical‐sensor pressure wire were prospectively evaluated in an all‐comer population with 50% to 99% lesions and ischemic FFR (≤0.80; ClinicalTrials.gov identifier NCT03227588). FCI was attempted in 250 vessels in 226 consecutive patients. The PCI success rate was 99.6% (249/250 vessels). FCI technical success—that is, FFR before and after PCI and PCI itself using the FFR wire—was 92% (230/250 vessels). Incidence of residual ischemia in the treated vessel was 36.5%. Approximately a third of these vessels (34.5%, n=29) were considered appropriate for further intervention, with FFR increasing from 0.71±0.07 to 0.81±0.06 ( P <0.001). Pressure wire pullback showed FFR ≤0.8 at distal stent edge was 7.9% and 0.7% proximal to the stent. FFR increase across the stent was larger in the ischemic than in the nonischemic group (0.06 [interquartile range: 0.04–0.08] versus 0.03 [interquartile range: 0.01–0.05]; P <0.0001) compatible with stent underexpansion as a contributor to residual ischemia. Conclusions FCI is a feasible and safe clinical strategy that identifies residual ischemia in a large proportion of patients undergoing angiographically successful PCI. Further intervention can improve ischemia. The impact of this strategy on long‐term outcomes needs further study.

scholarly journals CMET-22. CAPMATINIB (INC280) IN METΔEX14-MUTATED ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC): EFFICACY DATA FROM THE PHASE 2 GEOMETRY MONO-1 STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi56 ◽  
Author(s):  
Rebecca S Heist ◽  
Takashi Seto ◽  
Ji-Youn Han ◽  
Noemi Reguart ◽  
Edward B Garon ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Ad Hoc ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
New Treatment ◽  
Line Of Therapy ◽  
Ecog Ps ◽  
Nsclc Patients

Abstract BACKGROUND Capmatinib is a highly potent, selective MET-inhibitor known to cross the BBB, and intracranial activity with capmatinib has been previously reported. Updated results for overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and brain metastases (BM) activity from the GEOMETRY mono-1 study are presented here. METHODS GEOMETRY mono-1 is a phase 2, multi-cohort, multicenter study evaluating capmatinib in METΔex14-mutated or MET-amplified NSCLC patients. Patients (≥18 years) with ECOG PS 0–1, ALK-/EGFR-wt, and stage IIIB/IV NSCLC were eligible. Patients with asymptomatic BM were allowed. METΔex14-mutated patients were assigned to Cohorts 4 (1–2 prior lines of treatment) and 5b (treatment-naive) and received capmatinib 400mg BID. Endpoints by BIRC: ORR (primary, RECIST v1.1), DOR, and PFS. Ad hoc BIRC neuro-radiologic assessments of all Cohort 4 and 5b patients with baseline BM were performed. RESULTS As of April 15, 2019, 97 patients (Cohort 4: 69 patients; Cohort 5b: 28 patients) were evaluable for efficacy. BIRC assessments: ORR (95%CI): 40.6% (28.9–53.1) in Cohort 4; 67.9% (47.6–84.1) in Cohort 5b. Median DOR (95%CI): 9.7 (5.55–12.98) and 11.1 (5.55-NE) months and median PFS (95%CI): 5.4 (4.17–6.97) and 9.7 (5.52–13.86) months for Cohorts 4 and 5b, respectively. Of 13 evaluable patients with BM at baseline, 7 (54%) had intracranial response by BIRC, including 4 patients with complete resolution of brain lesions, and 12/13 had intracranial disease control. Responses in the brain were as fast as systemic responses. Most common treatment-related AEs (≥15%, all grades) across all cohorts (N=334): peripheral edema (41.6%), nausea (33.2%), increased blood creatinine (19.5%), and vomiting (18.9%); most AEs were grade 1/2. CONCLUSION These data confirm capmatinib to be a promising new treatment option for patients with METΔex14-mutated advanced NSCLC regardless of line of therapy, with deep and durable responses including in patients with brain metastases, and a manageable toxicity profile.

Disease stabilization (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) or gefitinib (G)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18115-18115 ◽  
Author(s):  
P. Pronzato ◽  
M. Loprevite ◽  
A. Brianti ◽  
C. Defferrari ◽  
G. Catania ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Pooled Data ◽  
First Line Therapy ◽  
Mutational Status ◽  
Best Response ◽  
Open Label Phase ◽  
Disease Stabilization ◽  
Nsclc Patients

18115 Background: One retrospective study (Hotta K, Ann Oncol 2005), investigating the prognosis of patients (pts) obtaining SD as best response with G treatment, has demonstrated that both progression-free survival (PFS) and survival (S) were significantly longer than those in pts with progressive disease (PD). The aim of this retrospective study was to compare the PFS and S outcome in pts with advanced NSCLC who achieved SD or partial response (PR) after treatment with E or G. Methods: Pooled data from 62 pts, entered into an open label phase II program of E (n=31) and a compassionate-use program of G (n=31), were retrospectively analyzed. E and G were given orally at 150 and 250 mg per day respectively and were continued until disease progression, development of unacceptable toxicity or patient’s refusal. Results: Pts characteristics: median age 69 years (42–85); females= 21 pts (34%); never/former smokers= 16/38 pts (26/61%); adenocarcinoma/BAC= 35/10 pts (56/16%); PS 0/1= 18/38 pts (29/61%). In 16 pts (26%) E or G were given as first-line therapy; 21 pts (34%) had received =2 prior lines of chemotherapy. Six pts (10%) achieved a PR and 18 pts (29%) obtained SD. TTP and OS in pts obtaining PR and SD were comparable: 7 vs 5.5 and 9.7 vs 9.1 months respectively. In progressing pts median TTP and OS were 1.7 and 3.7 months. Conclusions: Our findings indicate the importance of achieving disease control with both E and G treatment. Pts obtaining SD had a similar PFS and S compared with those having PR. An analysis of the role of mutational status and other biomarkers in predicting clinical outcome is currently underway. No significant financial relationships to disclose.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

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