Does RECIST-defined progression correlate with lack of further sunitinib (SU) benefit in advanced renal cell carcinoma (aRCC)?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15093-e15093
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Stable Disease ◽  
Clinical Benefit ◽  
Radiographic Progression ◽  
Clinical Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Risk Groups ◽  
Complete Response ◽  
Disease Response ◽  
Kaplan Meier

e15093 Background: RECIST defined radiographic progression on SU may be confounded by the intermittent dosing schedule and scan timing. Response rates to second line agents are typically lower and of shorter duration We analysed the potential for continued clinical benefit from continuation on Sunitinib following RECIST-defined progression in selected pts . Methods: Our institutional database was reviewed to identify aRCC pts who: 1) received SU, 2) achieved response or stable disease, and 3) had continuation of SU after documentation of RECIST-defined progression. Treatment history was obtained from medical chart review. CT scans were retrospectively assessed by RECIST criteria, pattern of progression was documented. SU cessation reasons were identified. Progression-free survival (PFS), post-progression treatment duration (PPD) and overall survival (OS) estimated by Kaplan Meier method. Results: Of 39 patients (pts) treated with SU between 2006 and 2009, 13 met entry criteria. Median age was 62 years (range: 33 – 66) with 11(85%) males. Eleven (85%) had prior nephrectomy and 4 (31%) had prior immunotherapy. Number of pts with MSKCC good/intermediate/poor risk groups were 5/7/1. Best radiographic response achieved was complete response/partial response/stable disease in two, five and six pts. Median PFS was 16.4 mos (11.8 – 23.8). Seven (54%) had progression of existing lesions while the six developed new lesions. Pts continued on SU as progression was relatively minor and clinical status was maintained. Median PPD was 4.2 months (0.6 – 40.5). Most common reasons for SU cessation were on-going radiographic progression (71%) and toxicity (18%). Only 2 pts stopped SU secondary to clinical deterioration. 62% of pts received subsequent lines of treatment, with half receiving 3rd line therapy. Median OS for the cohort was 31.7 mos. Conclusions: Continuation of treatment with SU following RECIST progression appears feasible and safe with prolonged disease control in selected pts . This approach should be further validated prospectively in a larger patient cohort. In this group, current standards for disease response assessment may underestimate the duration of clinical benefit conferred.

Analysis of toxicity and clinical outcomes (CO) in full versus reduced dose cabozantinib (cabo) in metastatic renal cell carcinoma (mRCC) patients (pts).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 671-671
Author(s):  
Dylan J Martini ◽  
Julie M. Shabto ◽  
Yuan Liu ◽  
Bradley Curtis Carthon ◽  
Alexandra Speak ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Clear Cell ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Reduced Dose ◽  
Kaplan Meier

671 Background: The full dose of cabo is 60 mg, but some pts are treated with a reduced dose with the clinical anticipation of adverse events (AEs). We compared AEs and CO in mRCC pts treated with full versus reduced dose cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016-2018. CO were measured by overall survival (OS), progression-free survival (PFS), and objective response (OR). OS and PFS were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. OR was defined as partial response (PR) or complete response (CR) per RECISTv1.1. AEs were collected from clinic notes. Univariate analysis (UVA) of association between AEs and CO was performed using logistic regression model. Results: Most pts were males (68%) and the median age was 63 years. Most (79%) had clear cell RCC (ccRCC) and the majority were IMDC intermediate (59%) or poor (39%) risk. Most pts (68%) received 60 mg and 48% of these pts underwent a dose reduction for AEs. Nearly all pts (95%) who started on a reduced dose experienced AEs, compared to 66% for pts treated with 60 mg. OR rate was similar for pts on 60 mg (18%) and pts on a reduced dose (19%). The median survival was comparable in pts treated with 60 mg and pts treated with a reduced dose (10.9 vs. 8.8 months, p=0.92 for OS and 5.6 vs. 5.1 months, p=0.23 for PFS) per Kaplan Meier estimation. AEs, particularly gastrointestinal (GI) AEs, were associated with significantly lower chance of OR (Table). Conclusions: CO may be comparable in mRCC pts treated with full versus reduced dose of cabo, but a reduced dose of cabo may not be associated with decreased AEs. GI side effects may be a poor prognostic factor in mRCC pts treated with cabo. Larger studies are warranted to validate these findings. [Table: see text]

Phase II trial of robotic stereotactic radiosurgery (SBRT) in patients with recurrent gynecologic malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5102-5102
Author(s):  
Charles Kunos ◽  
James Brindle ◽  
Ramon Adams ◽  
Robert DeBernardo
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Stable Disease ◽  
Clinical Benefit ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Benefit Rate

5102 Background: Ablative radiation dose delivered by a robotic SBRT platform has shown progression-free survival benefit in two limited case series among patients with recurrent gynecological malignancies. The therapeutic impact of SBRT on disease progression (PD) was evaluated in the recurrent setting in this phase II trial. Methods: Fifty patients with recurrent and measurable gynecologic malignancy were treated with SBRT. The cohort included patients with recurrent ovarian (n =25), endometrial (n =14), cervical (n =9), or vulvar (n =2) cancer, 1 prior chemotherapy or radiation regimen, and GOG performance status 0, 1, 2. Patients underwent image-guided SBRT in 3 daily doses of 800 cGy = 2400 cGy. SBRT planning target volumes were determined by both the radiation and gynecologic oncologist using non-contrasted CT and 18F-FDG PET/CT overlays. The primary endpoints were 6-month clinical benefit rate (# complete response + # partial response + # stable disease without PD [by RECIST v1.0] / 50), and less than 30-day posttherapy toxicity. Results: Between July 2009 and September 2011, 50 patients were enrolled and have a median posttherapy follow-up of 9 months. At 3 months, 50% (n=25) had complete response, 46% (n=23) had partial response, and 4% (n=2) had stable disease in SBRT-targeted lesions. Twenty-six patients (52%) have had non-SBRT target PD and 18 (36%) have died of PD. Of the 50 patients, 33 had a PD-free interval of at least 6 months, for an overall clinical benefit rate of 66%. Less than 30-day posttherapy SBRT-related toxicities were grade 2 fatigue (n =9 [18%]), grade 2 nausea (n =3[6%], grade 3 nephropathy (n =2[4%]), and grade 4 hyperbilirubinemia (n =1[2%]). Conclusions: This is the first phase II clinical trial of SBRT showing a clinically relevant benefit of ablative radiation in the setting of recurrent gynecological disease. Despite excellent control of targeted lesions with minimal toxicity, non-SBRT target PD rates are high, spurring interest for future SBRT-chemotherapy clinical trials.

Erlotinib has activity in androgen-independent prostate cancer (AIPC) patients who are chemotherapy-naive: A phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15606-15606 ◽  
Author(s):  
C. Nabhan ◽  
K. Tolzien ◽  
S. Newman ◽  
S. Kelby ◽  
T. Lestingi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Stable Disease ◽  
Clinical Benefit ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Response Assessment ◽  
Complete Response ◽  
Clinical Activity ◽  
Study Results

15606 Background: Mechanisms of hormone resistance for AIPC are variable. One proposed mechanism is the over expression of the epidermal growth factor receptor (EGFR) which in turn stimulates proliferation through its pathway. We aimed to determine the efficacy of an oral anti-EGFR inhibitor (erlotinib) in this patient population that was chemotherapy-naive. The primary end point was to evaluate the overall clinical benefit defined as the sum of complete response (CR), partial response (PR), and stable disease (SD). Methods: Between January and December 2006, sixteen patients were enrolled onto this phase II study. Median age was 78 years (66–85). Median PSA was 61.9 (9.2–800.2). Median time from initial diagnosis until starting Erlotinib was 7.8 years. Erlotinib was given daily at 150 mg until disease progression. Patients were evaluated every 2 weeks for toxicity. Response assessment took place every 2 cycles (each cycle was 4 weeks). Evaluations included computed tomography of measurable disease areas, bone scans, and serum PSAs. Patients who progressed radiographically but maintained a PSA response or those who progressed biochemically but maintained a radiographic response were considered stable and were allowed to continue on study. Results: Sixteen patients were enrolled with 14 being evaluable at this time (2 patients are early in their course). Median cycles received is 2 (range 1.5–12). One patient achieved a PR and continues on Erlotinib after one year of enrollment. Three patients demonstrated stable disease but two of them later progressed. One patient withdrew after 9 days of starting therapy due to fatigue and poor taste. All other patients developed disease progression after two cycles of therapy. The calculated overall clinical benefit was 28% (4 responses out of 14 patients). One patient died from pneumonia and seizures unrelated to Erlotinib as confirmed by an autopsy that showed progression in the central nervous system. Erlotinib was well-tolerated with skin rash and diarrhea being the most common toxicities. Conclusions: Erlotinib has clinical activity as a single agent in AIPC. Updated results of this ongoing study will be presented at the meeting. Further studies with this agent alone or in combination are warranted. No significant financial relationships to disclose.

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Primary Analysis ◽  
Open Label ◽  
Secondary Endpoints ◽  
To Receive ◽  
Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

NIMG-54. RADIOMIC FEATURES FROM LESION HABITAT PREDICT RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: A FEASIBILITY STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi141-vi141
Author(s):  
Ruchika Verma ◽  
Yasmeen Rauf ◽  
Ipsa Yadav ◽  
Volodymyr Statsevych ◽  
Jonathan Chen ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Poor Response ◽  
Response Assessment ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Expert Radiologist ◽  
Mri Scans

Abstract PURPOSE The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab. METHODS Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS). RESULTS CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656). CONCLUSION Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.

Outcome of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral cavity squamous cell carcinoma (SCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18034-e18034
Author(s):  
Lakhan Kashyap ◽  
Vijay Maruti Patil ◽  
Sachin Dhumal ◽  
Vanita Noronha ◽  
Amit Joshi ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Infratemporal Fossa ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Oral Tongue ◽  
Resection Rate ◽  
Kaplan Meier

e18034 Background: NACT is often used in technically unresectable oral cavity SCC to improve resection rate. NACT regimen based on combination of maximum tolerated doses (MTD) and metronomic chemotherapy will debulk the tumor and subsequently inhibit angiogenesis which may overcome drug resistance of MTD schedule. We assessed outcome and tolerance of this combination as NACT in patients with technically unresectable oral cavity SCC. Methods: This is retrospective analysis of prospectively maintained data. Fourteen patients having technically unresectable oral cavity SCC received NACT with paclitaxel (175mg/m2) plus carboplatin (AUC5) every 3 weekly (MTD schedule) and OMCT (methotrexate 9mg/m2 once a week, celecoxib 200mg twice daily and erlotinib 150mg once daily). Patient were assessed clinically and radiologically after minimum of two cycles for surgery. Kaplan-Meier method was used for survival analysis. We report resectability, survival and tolerance of this regimen. Results: Median age of the patients was 38 years, and twelve patients (85%) were male. Twelve (85%) and two (15%) patients had buccal mucosa and oral tongue primary, respectively. AJCC 2017 stage IVA and IVB disease was present in twelve (85%) and two (15%) patients, respectively. Reason for technical unresectabilty was skin edema above zygoma in five (36%), high infratemporal fossa involvement in five (36%), nodal encasement of major vessels in two (14%) and posterior extent of oral tongue tumor into oropharynx in two (14%) patients. Median number of NACT administered were three. Tumor of nine patients (65%; 95% CI = 39%-89%) were deemed resectable after NACT. Eight patients underwent surgery and tumor of one patient showed pathologic complete response. Median follow up was 14.6 months (95% CI = 14.1 - 15 months). Median progression free survival was 11.4 months (95% CI = 7.9 – 15 months). Median overall survival (OS) was not reached while OS at 15 months was 63.5% (95% CI = 37.8% - 89.2%). Common grade 3/4 toxicities (CTCAE 5.0) were neutropenia in eight (57%), thrombocytopenia in three (21%), febrile neutropenia, hypokalemia and diarrhoea in two patients (14%) each. Two patients required in-patient supportive care for adverse events. Conclusions: Paclitaxel and carboplatin along with OMCT is well tolerated and less resource intensive regimen which leads to favorable resection rate and survival in patients with technically unresectable oral cavity SCC.

A randomized trial comparing cisplatin plus cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

1986 ◽  
Vol 4 (6) ◽  
pp. 965-971 ◽  
Author(s):  
P F Conte ◽  
M Bruzzone ◽  
S Chiara ◽  
M R Sertoli ◽  
M G Daga ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Median Survival ◽  
Stable Disease ◽  
Residual Disease ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Second Look

After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) (corrected) or PAC (PC + doxorubicin 45 mg/m2). After six cycles, patients clinically disease-free or with resectable residual disease were submitted to second-look surgery. After restaging, patients in surgical complete response (CR) stopped treatment while those responding partially (PR) received six more courses; patients whose disease progressed were excluded from the study. Among patients with measurable disease, the following clinical response rates were observed: PC = 20% CR, 34.3% PR, 14.3% stable disease, and 31.4% progression; PAC = 40.6% CR, 15.6% PR, 12.5% stable disease, and 31.3% progression. In the 75 patients submitted to second look, the results have been the following: PC = 39.5% CR, 36.8% PR, 7.9% stable disease, and 15.8% progression; PAC = 62.2% CR, 18.9% PR, 10.8% stable disease, and 8.1% progression. The difference in surgical complete response in favor of the PAC regimen is significant (P less than .05). Median survival and progression-free survival were 800 and 400 days, respectively, for PAC arm; median survival and progression-free survival were 680 and 380 days, respectively, for PC. These differences are not significant. Probability of survival was affected by FIGO stage, amount of residual disease, histology, performance status, and response at second look, while no influence was observed according to grade of tumor differentiation and age. Our results demonstrate the usefulness of doxorubicin in terms of surgical CR.

Complete response (CR) to ifosfamide, gemcitabine, and vinorelbine (IGEV) and outcome in relapsed/refractory Hodgkin's lymphoma (HL) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8568-8568
Author(s):  
A. Anastasia ◽  
R. Mazza ◽  
L. Giordano ◽  
M. Balzarotti ◽  
M. Magagnoli ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Disease Status ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cox Proportional Hazard ◽  
Kaplan Meier

8568 Background: High dose chemotherapy with autologous stem cells transplant (ASCT) is the gold standard in patients with relapsed/refractory HL. Response to induction chemotherapy (chemosensitive patients) plays a major role in prognosis, however the role of CR status after induction therapy has not been established. Methods: One hundred twenty one patients with relapsed/refractory HL received 4 courses of IGEV followed by single (N=59) or tandem (N=19) ASCT (Santoro et al., Haematologica 92, 2007). Response to IGEV was evaluated by Cheson criteria (1999).The aim of this study was to evaluate the role of CR versus no-CR to IGEV induction therapy on the outcome in terms of progression free survival (PSF) and overall survival (OS). Statistical analysis was performed by using the Kaplan-Meier method and Cox proportional hazard model. Results: IGEV induced an overall response rate of 75% with 46% of CR. In the univariate analysis favourable factors for outcome were CR vs no-CR to IGEV (PFS: p <0.001, OS: p 0.002), A vs B symptoms (PFS: p 0.003; OS: p 0.05), limited vs advanced stage (PFS: p 0.03; OS: p 0.03), and 1 vs≥2 previous chemotherapy lines (PFS: p 0.03, OS: p 0.02); response to last therapy (relapsed vs refractory) influenced PFS (p 0.03) but not OS (p 0.70). The multivariate analysis confirmed the favourable prognostic role of CR to IGEV (PFS HR: 2.5, CI 95%:1.3; 4.6 - OS HR 2.3, CI 95%:1.1;4.8) and of the number of previous chemotherapy lines (PFS HR:1.8, CI 95%:1.0;3.2 - OS HR 2.1, CI 95%:1.1;3.9). Conclusions: According to our data, we conclude that: 1. CR to IGEV is the strongest indicator of outcome in relapsed/refractory HL. 2. Achievement of CR to IGEV overcomes the role of initial disease status. 3. Efforts are warranted to increase the CR rate by induction therapy. No significant financial relationships to disclose.

Biweekly gemcitabine and capecitabine in heavily pretreated patients with metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14617-e14617
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Paula Jiménez ◽  
Laura Faez Garcia ◽  
Carlos Alvarez Fernandez ◽  
Quionia Pérez Arnillas ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Clinical Benefit ◽  
Performance Status ◽  
Complete Response ◽  
Rank Test ◽  
Major Mechanism ◽  
Kaplan Meier ◽  
Hand Foot Syndrome ◽  
Heavily Pretreated ◽  
And Function

e14617 Background: Some patients with mCRC are still susceptible to continue with active therapy after progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens due to their good performance status. Preclinical and clinical trials suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. Their major mechanism of action is to incorporate dFdCTP into DNA and to introduce FUTP into RNA, respectively, affecting their processing and function. This study aims to describe patients profile and response to gemcitabine-capecitabine (GemCap) in heavily pretreated mCRC, and so possible predictive factors for survival. Methods: Between June 2001 and July 2011, 119 evaluable patients pretreated with oxaliplatin and irinotecan regimens were enrolled: ECOG 0-1 97%, male 68%, median age 63yo, range: 36-79, rectum 57%, 3rd line: 61%. Patients received Gem 1000 mg/m2 d2 and Cap 1000 mg/m2BID x 7d q2w. Survival analysis was determined by Kaplan-Meier and log-rank test. Results: ORR and clinical benefit were: 5% and 36%. Median PFS and OS were 2.83m (0.43-35) and 6.53m (0.47m-10yrs in patient with complete response). Most frequent toxicities were anemia (22%), thrombocytopenia (10%), hand-foot syndrome (9%) and grade ≥3 were diarrhea in 5%. There were no treatment-related deaths. Predictive factors for PFS and OS are shown in Table. Statistic significance was registered in favor of clinical benefit achieved and for those who had not previously received monoclonal Abs, for SLP and OS respectively. Moreover, patients under 65yo tend to have a better survival. Conclusions: These data suggest GemCap is a tolerable regimen that achieves maintained responses for non selected heavily preated mCRC patients, especially in those reaching radiological clinical benefit, without previous use of monoclonal Abs and younger patients. [Table: see text]

Association of immune-related adverse events (irAEs) with improved clinical outcome in sarcoma patients treated with immune checkpoint blockade (ICB).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11510-11510 ◽  
Author(s):  
Evan Rosenbaum ◽  
Kenneth Seier ◽  
Ciara Marie Kelly ◽  
Hannah Kiesler ◽  
Moriah Martindale ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Improved Outcomes ◽  
Comparison Results ◽  
Category Comparison ◽  
Grade 3

11510 Background: IrAEs are associated with improved clinical outcomes after treatment with ICB in select epithelial malignancies. We hypothesized that sarcoma patients (pts) treated with ICB who developed an irAE would have improved outcomes compared to pts who had no irAE. Methods: Adverse events (AEs) from 3 sarcoma-specific ICB trials (nivolumab plus NKTR-214, pembrolizumab plus epacadostat, and pembrolizumab plus T-VEC) were reviewed. AEs probably or definitely related to ICB were classified as immune- or non-immune-related by the principal investigator. Endpoints of interest included best overall response (BOR) by RECIST 1.1 (complete response [CR]/partial response [PR]), durable clinical benefit (DCB; CR/PR/stable disease [SD] ≥ 16 weeks), and progression-free survival (PFS). Outcomes were stratified by the presence or absence of ≥ 1 irAE of any grade and by grade 1-2, grade 3-4, or no irAE (three-category comparison). Results: A total of 124 pts received ICB on these studies. Median pt age was 56 (range: 13-90); 53% were male; all but one pt had a performance status of ≤ 1. BOR was PR in 12 pts, SD in 41, and PD in 69. 2 pts were not evaluable. 40 pts (32%) had ≥ 1 irAE of any grade, 6 of whom had a grade 3-4 irAE. The most common irAEs (≥ 5% of pts) were rash (15%), arthralgia (11%), myalgia (9%), pruritis (8%), and hypothyroidism (6%). The proportion of pts with a CR/PR was higher in pts with than without an irAE (18% vs. 6%, respectively; P = 0.058). A significantly higher proportion of pts with an irAE had DCB compared to those without (53% and 29%, respectively; P = 0.017). The median PFS of pts with an irAE was 16.6 months compared to 10.6 in those without (P = 0.013). The proportion of pts with a grade 3-4 irAE and a CR/PR was highest (33%) compared to pts with grade 1-2 (15%) or no irAE (6%) (P = 0.048). More pts with grade 3-4 irAE achieved DCB (67%) than grade 1-2 (50%) or no irAE (29%) (P = 0.027). Median PFS was 22.6, 15, and 10.6 weeks in the grade 3-4, grade 1-2, and no irAE groups, respectively (P = 0.047). Conclusions: Approximately one-third of advanced sarcoma pts with ICB-based immunotherapy developed an irAE. As reported previously in select carcinomas, sarcoma pts with irAEs were more likely to have clinical benefit than those without irAEs. Further research is needed to understand the mechanism behind this association and to validate these findings prospectively.

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