Rationale for the utilization of biological targeted agents (bTAs) in the treatment of metastatic colorectal cancer (mCRC), single tertiary cancer center experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15589-e15589
Author(s):  
Ivan Barrera ◽  
Yahia A. Lakehal ◽  
Tomas Kavan ◽  
Petr Kavan
Keyword(s):  
Bowel Perforation ◽  
Primary Objective ◽  
Cancer Center ◽  
Gi Symptoms ◽  
Significant Difference ◽  
Common Grade ◽  
Jewish General Hospital ◽  
Grade 3 ◽  
Physician Patient ◽  
Tertiary Cancer Center

e15589 Background: Worldwide treatment for 1st line (1LTx) mCRC included doublet or triple chemotherapy with or without bTAs. In Quebec, the anti-EGFR therapy (panitumumab or cetuximab) was only recently approved in this setting for patients RAS WT, Bevacizumab (B) not eligible. In this study we evaluated the rational and outcomes using bTAs. Methods: Retrospective study assessing mCRC pts treated with or without bTAs at any time throughout the course of therapy at the Jewish General Hospital between 2010-2018. Pts were divided in 3 groups according to their 1LTx for analysis: Chemotherapy alone (1LChA), Chemotherapy plus B (1LChB), and anti-EGFR with or without chemotherapy (1LaEGFR). The primary objective was to assess the rational of bTAs prescription based in 1LTx selection. Secondary objectives included safety, PFS and OS. Results: Among a total of 463 pts with mCRC; 196 pts (42.3%) received 1LChA, 246 pts (53.2%) 1LChB, and 21 pts (4.5%) 1LaEGFR respectively. 1LChA group, 51% omitted bTAs for physician-patient preferences, 96 pts (49%) had contraindications for B, and 79 pts (40.3%) were potentially candidates for aEGFR, but did not receive it. 152/196 (77.5%) pts continued to 2LTx and 34.8% received bTAs. As for the 3LTx, 78/196 (40%) received a treatment, 48.7% received bTAs. The most common grade 3-4 adverse events (AEs) were hypertension and bowel perforation in B, gastrointestinal (GI) symptoms and skin reaction (SR) in aEGFR. 1LChB group, 31 pts (12.6%) presented AEs related to B. 191/246 pts (77.6%) continued to 2LTx with 48 pts (25%) receiving ChB despite progression in 1LTx on this bTA and 19 pts (10%) receiving aEGFR. The most common AEs reported in 2LTx were GI symptoms and neuropathy. In 3LTx, 54/91pts (59.3%) received aEGFR therapy and 8 pts (14.8%) had SR AEs. 46 pts (18.6%) continued to 4LTx, 13/46 pts (28.2%) received aEGFR. 1LaEGFR group, the most common AEs were SR and GI symptoms. 11/21 pts (52.3%) continued to 2LTx; 5 pts (45.4%) switching bTA class and receiving ChB. 81% pts started treatment between 2017-2018 and had at least two contraindication criteria for. The median PFS for the 1LChA and 1LChB groups were 10 and 11.5 months, respectively, and were not statistically significant (p=0.22). The OS with 1LChA and 1LChB was 33.26 vs. 27.80 months (p=0.27). The PFS and OS between 1LChA and 1LaEGFR were 10 vs 11 months (p= 0.27) and 33.26 vs. 35.07 months (p=0.13). Conclusions: The outcome and tolerability of bTAs in mCRC appear similar in our institution and randomised trials. We were not able to detect any significant difference among the three groups of comparison. The 1LaEGFR available data in this subset of patients are limited. Our data highlights the importance of optimal therapeutic sequencing to prolong OS. Dedicated studies are needed in order to determine the best bTAs therapeutic strategy in mCRC.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

Effects of proton pump inhibitors (PPIs) on FOLFOX and XELOX regimens in colorectal cancer (CRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 621-621
Author(s):  
Grace Wong ◽  
Vincent Ha ◽  
Michael Patvin Chu ◽  
Deonne Dersch-Mills ◽  
Sunita Ghosh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Retrospective Chart Review ◽  
Primary Objective ◽  
Stage Ii ◽  
Cancer Center ◽  
Significant Difference

621 Title: Effects of Proton Pump Inhibitors (PPIs) on FOLFOX and XELOX Regimens in Colorectal Cancer (CRC) Background: First-line adjuvant chemotherapy options for stage II-III CRC include XELOX (capecitabine (cape), oxaliplatin) and FOLFOX (oxaliplatin, leucovorin, 5FU). Cape is an oral 5FU prodrug, and recent studies suggested that PPIs may detrimentally affect cape efficacy. Conversely, some literature posits that PPIs may negatively impact CRC itself. Our primary objective was to compare 3-year recurrence-free survival (RFS) rates between XELOX-treated PPI-users and non-PPI users, and FOLFOX-treated PPI users and non-PPI users. Our main secondary objective was to compare overall survival (OS). Methods: We conducted a retrospective chart review of 389 stage II-III CRC patients (pts) who received adjuvant XELOX or FOLFOX from a tertiary cancer center in Alberta, Canada between 2004-2013. Information regarding PPI use, cancer treatment, and pt outcomes were gathered and analyzed from pharmacy databases. Results: 23.4% of XELOX-treated pts and 28.0% of FOLFOX -treated pts used PPIs concurrently with treatment. 3-year RFS was significantly lower in XELOX-treated PPI pts than non-PPI pts (69.5 vs. 82.6%, P=0.029). Unadjusted analysis showed that XELOX-treated PPI pts were twice as likely to experience cancer recurrence or death as XELOX-treated non-PPI pts (HR 2.03, P=0.033). FOLFOX-treated PPI pts had a non-significant increase in three-year RFS versus non-PPI pts (82.9 vs. 61.7%, P=0.066), and no significant difference in recurrence or death (HR 0.51, P=0.071). No significant differences were seen in OS. Conclusions: Our results suggest that PPIs negatively impacted RFS in early-stage XELOX-treated CRC pts, and yielded no significant effect amongst FOLFOX-treated patients. Further studies are required to corroborate our findings. [Table: see text]

Pemetrexed and carboplatin plus bevacizumab for advanced non-squamous non-small cell lung cancer (NSCLC): Preliminary results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7601-7601 ◽  
Author(s):  
J. D. Patel ◽  
T. A. Hensing ◽  
V. Villafor ◽  
E. Hart ◽  
P. Bonomi
Keyword(s):  
Bowel Perforation ◽  
Previous History ◽  
Median Number ◽  
Hematological Toxicity ◽  
Prior History ◽  
Toxicity Profile ◽  
Common Grade ◽  
History Of ◽  
Grade 3 ◽  
Number Of Cycles

7601 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity and favorable toxicity profile in NSCLC. Bevacizumab has been shown to improve response rates and survival in pts with advanced non-squamous NSCLC when combined with carboplatin and paclitaxel. This study of pemetrexed and carboplatin plus bevacizumab was designed to evaluate the toxicity profile and to estimate the activity of the regimen in this pt population. Methods: Eligibility required that pts were chemotherapy-naive, had stage IIIB (effusion)/IV non-squamous NSCLC, PS 0–1, with no evidence of CNS metastases. Pts received pemetrexed 500 mg/m2 over 10 minutes, carboplatin AUC 6 over 30 minutes, and bevacizumab 15 mg/kg over 30–90 minutes on a 21-day cycle for 6 cycles. Pts with SD or PR received pemetrexed 500 mg/m2 and bevacizumab 15 mg/kg every 21 days until disease progression or toxicity. All pts received folic acid, vitamin B12 and steroid prophylaxis. Results: From 8/05 to 9/06, 39 pts (of planned 50) were enrolled: 20 M/19 F; median age 64 (range 41 - 80). One pt enrolled and subsequently refused treatment. Median number of cycles was 6 (range 1–22), and 25/38 (66%) completed at least 6 cycles of therapy. There was no grade 4 hematological toxicity. Grade 3 hematological toxicities were anemia (5%, N=2) and thrombocytopenia (3%, N=1). The most common grade 3/4 non-hematological toxicities included proteinuria (3%, N=1, gr 3), venous thrombosis (3%, N=1, gr 3), infection (3%, N=1, gr 4), and diverticulitis (11%: 8%, N=3, gr 3/3%, N=1, gr 4). 1 pt with diverticulitis experienced bowel perforation that required surgical intervention. The trial was temporally suspended and the group of pts with diverticulitis was analyzed separately. The only risk factor identified was previous history of diverticulitis. One CR, 20 PRs were observed for an overall response rate of 55% (95%, CI 43–75%). Conclusions: Treatment with pemetrexed and carboplatin plus bevacizumab in pts with advanced non-squamous NSCLC is feasible with an acceptable toxicity profile. The encouraging activity justifies further development of this regimen. However, pts with a prior history of diverticulitis should be excluded until this observation can be investigated further. No significant financial relationships to disclose.

Adavosertib with chemotherapy (CT) in patients (pts) with platinum-resistant ovarian cancer (PPROC): An open label, four-arm, phase II study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5513-5513 ◽  
Author(s):  
Kathleen N. Moore ◽  
Setsuko K. Chambers ◽  
Erika Paige Hamilton ◽  
Lee-may Chen ◽  
Amit M. Oza ◽  
...  
Keyword(s):  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Primary Objective ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

5513 Background: Adavosertib (AZD1775; A), a highly selective WEE1 inhibitor, demonstrated activity and tolerability in combination with carboplatin (C) in primary PROC. This study (NCT02272790) assessed the objective response rate (ORR) and safety of A in PROC. Methods: Pts with recurrent RECIST v1.1 measurable PROC received A with C, gemcitabine (G), weekly paclitaxel (P), or pegylated liposomal doxorubicin (PLD) in 3- (C) or 4-week (G, P, PLD) cycles (Table). Tumor assessments were performed every 2 cycles until disease progression. Primary objective: ORR; other objectives: disease control rate (DCR), progression-free survival (PFS) and safety. Results: In the 94 pts treated (median treatment duration 3 months; range 0–16 months), outcomes were greatest with A (weeks [W]1–3) + C (Table), with ORR of 67% and median PFS (mPFS) of 10.1 months for this cohort. Most common grade ≥3 treatment-emergent adverse events (TEAEs) are shown in the Table, with hematologic toxicity most notable with A (W1–3) + C. TEAEs led to A dose interruptions, reductions and discontinuations in 63%, 30% and 13% of the whole cohort, respectively. A possible positive relationship between CCNE1 amplification and response warrants further investigation. Conclusions: A shows preliminary efficacy when combined with CT. Pts receiving A (W1–3) + C showed greatest benefit. The increased but not unexpected hematologic toxicity is a challenge and could be further studied to optimize the dose schedule and supportive medications. Clinical trial information: NCT02272790. [Table: see text]

Incidence and severity of systemic allergic reactions (SAR) reported with chemotherapeutic drugs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18802-e18802
Author(s):  
Beulah Elsa Thomas ◽  
Anju Murugan ◽  
Hrishi Varayathu ◽  
Lalram Sangi ◽  
Sonia Rani ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Complete Response ◽  
Cancer Center ◽  
Grading System ◽  
Grade Classification ◽  
Grade 5 ◽  
Dose Number ◽  
Grade 3 ◽  
Tertiary Cancer Center

e18802 Background: SAR, a known adverse event of cancer therapy has variable severity. Despite the availability of many approved grading tools, there is still a lack of a globally applicable grading system. To address this, World Allergy Organization (WAO) created a uniform 5-grade classification system which was modified recently to be applicable for all SAR’s. This study aims to understand the incidence and severity of chemotherapy induced SAR and overall response rate (ORR) of rechallenged drugs in a tertiary cancer center. Methods: A retrospective single centered analysis of 103 patients with chemotherapy induced SAR was carried out. Patients were stratified based on age, gender, drugs given, dose number and severity of reaction. We used Modified WAO Grading System for assessing the severity. Descriptive statistics was applied to decipher the data. ORR is defined as the proportion of patients who have a partial or complete response to rechallenged drugs using RECIST Criteria for solid tumors and Lugano Classification for lymphoma. Results: Among 103 patients who reported SAR, 63.1% were female and 64.1% patients were less than 60 years of age. Among the 22 drugs, median dose number was high for Oxaliplatin (6) and Carboplatin (5). SAR was more observed with Paclitaxel (20.39%), Carboplatin (17.48%) and Rituximab (13.59%). However, carboplatin and rituximab had more incidence of grade 1 SAR(25.92% and 29.63% respectively). Grade 1 SAR (39.80%) were reported the highest followed by grade 3 (29.13%), grade 5 (13.59%), grade 2 (11.65%), and grade 4 (5.83%). Cetuximab precipitated the most grade 5 reactions (33.33%). Among patients exhibiting SAR with Paclitaxel, 42.86% were switched to alternatives, Nab-paclitaxel (28.57%) being preferred the most. Carboplatin was changed to cisplatin in 16.66% patients and Nanosomal docetaxel lipid suspension replaced docetaxel in 42.86% patients who reported SAR with carboplatin and docetaxel respectively. Rituximab was rechallenged the most (11.65%) off which one patient had reaction. ORR was observed to be 62.5% and 50% among rechallenged Paclitaxel and Rituximab respectively. The incidence of SAR is depicted in the below table. Conclusions: The study inferred that most SAR reactions occurred with Paclitaxel and Carboplatin. Oxaliplatin and Carboplatin presented with delayed SAR. Grade 1 and grade 3 reaction were relatively more. Cetuximab reported the most grade 5 reactions. ORR of rechallenged drugs should be monitored in further larger studies.[Table: see text]

Same-day pegfilgrastim or pegfilgrastim-cbqv prophylaxis in miniCHOP chemotherapy based regimens for non-Hodgkin lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19542-e19542
Author(s):  
Trace Bartels ◽  
Ali McBride ◽  
Neda AlRawashdh ◽  
Logan Moore ◽  
Daniel O Persky ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Study Groups ◽  
Primary Objective ◽  
Cancer Center ◽  
Safety And Efficacy ◽  
Non Hodgkin Lymphoma ◽  
University Of Arizona ◽  
Chemotherapy Dose ◽  
Grade 3 ◽  
The University

e19542 Background: Non-Hodgkin’s lymphoma, specifically, diffuse large B-cell lymphoma (DLBCL) is most frequently diagnosed among older patients. The utilization of a reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisone (miniCHOP) chemotherapy-based regimen has an improved tolerance and toxicity profile in select patient populations. Prophylaxis with pegfilgrastim or its biosimilar pegfilgrastim-cbqv is administration on the same day of chemotherapy in all patients with MiniCHOP at The University of Arizona Cancer Center (UACC). We report here on the first study to address the safety and efficacy of same day pegfilgrastim administration in lymphoma patients receiving MiniCHOP. Methods: A retrospective, single center, cohort study was conducted at UACC between October 1, 2013 and October 2020 to evaluate lymphoma patients who were treated with miniR-CHOP and given pegfilgrastim or its biosimilar (pegfilgrastim-cbqv) for FN prophylaxis. The primary objective was to compare the incidence of FN across all cycles of chemotherapy and after the first cycle of chemotherapy in DLBCL patients on miniR-CHOP and provided with next-day versus same-day pegfilgrastim administration. Our secondary outcomes of interests were incidence of chemotherapy-induced neutropenia (CIN) grade 3/4; hospitalization; anti-biotics administration; and chemotherapy dose-reduction or delays. Results: A total of 100 cycles of miniR-CHOP were received, of these pegfilgrastim was administered on same-day of chemotherapy in 95 cycles and five cycles on the next-day of chemotherapy. Among all cycles the incidence of FN was 5.3% vs. 0.0 ( P= 1.00); CIN 3/4 was 10.5% vs. 0.0 ( P= 1.00); hospitalization was 10.5% vs. 20.0% ( P= 0.45), anti-biotics administration was 6.3% vs. 40.0% ( P= 0.05) and the chemotherapy dose delays or reductions was 16.8% vs. 0.0% ( P= 0.99). In the first cycle of chemotherapy, the incidence of FN was 14.3% vs. 0.0% ( P= 1.00), CIN 3/4 was 21.4% vs. 0.0 ( P= 1.00), hospitalization 28.6% vs. 25.0% ( P= 0.99), and the anti-biotics administration was 21.4% vs. 50.0% ( P= 0.53) for same-day vs. next-day study groups. Conclusions: In our analysis, we have shown that same-day pegfilgrastim or pegfilgrastim-cbqv was safe and effective in lymphoma patients receiving miniR-CHOP. There was no significant increase in FN or delayed engraftment in either group. Future prospective studies are warranted to address the safety and efficacy profile of same day pegfilgrastim or a pegfilgrastim biosimilars in elderly lymphoma patients.

Voriconazole Increase the Risk of PN in Multiple Myeloma Patients Treated with Bortezomib-Based Chemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5394-5394
Author(s):  
Yan Xu ◽  
Shuhui Deng ◽  
Gang An ◽  
Zengjun Li ◽  
Xiaoqi Qin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Primary Objective ◽  
M Protein ◽  
Comparable Efficacy ◽  
Best Response ◽  
Median Dosage ◽  
Significant Difference ◽  
Grade 3

Abstract Background Bortezomib (btz) is the major and potent agent in multiple myeloma (MM) treatment and intravenous (IV) injection is its standard administration route. Our previous study showed that Subcutaneous (SC) administration of btz was an important alternative with comparable efficacy but better safety profile, significantly decreased and delayed the development of peripheral neuropathy (PN) in patients with MM. However, PN still always limited the use of btz. The primary objective is try to identify some correlative factors for PN, then to decrease the risk of PN and the grade of PN. Methods This retrospective study was undertaken at a single centre in China. Patients with NDMM were assigned to receive up to nine 21-day cycles of Btz based regimens, including PAd/VDd/BCd (btz 1.3mg/m2, on days 1, 4, 8 and 11; adriamycin 9mg/m2 intravenously on days 1 - 4; or PLD 30mg/m2, intravenously on days 1, or CTX 500mg/m2, orally on days 1, 8, 15, and dexamethasone 20mg/day, orally or intravenously on days 1, 2, 4, 5, 8, 9, 11 and 12). Btz was administered by SC injection or IV infusion. The basic characteristics, drug combination (especially drugs for fungi), the effect and adverse events were recorded. Then the correlation were analysed. Results 252 (male, n=159) NDMM patients were received Btz based treatment from Oct. 2008 to Nov. 2014. The median age were 56 (26-77). In this group, patients were treated with a median 4 cycles of btz-based chemotherapy. 98, 101 and 53 patients received PAd, BCd and VDd regimen, respectively. 114 patients received IV btz, and 148 received SC btz. The median total Btz dosage was 20.4 (2.6-56.6) mg/m2. Patients achieved at least PR at median 1 (1-7) cycle, and achieved the best response at median 2 (1-9) cycles. The overall response rate (ORR, >=PR) was 95%, with 33.3%, 12.4%, 22.4% achieved CR, nCR and VGPR, respectively. With median follow up 24 months, the median PFS and OS were 28 months, and not arrived, respectively. There was no significant difference between IV and SC group. During their course, 49, 19, 73, and 46 cases received fluconazole, itraconazole, voriconazole, and caspofungin respectively as prophylaxis or treatment for fungi. 140 (55.56%) patients developed PN during their courses, with 17.06% were ≥ grade 3. The median dosage of btz when PN developed was 15.6 mg/m2. In the subgroup which combined voriconazole, 59 (80.82%) patients developed PN, with 39.07% were ≥ grade 3. The median dosage of btz when PN developed was 12.3mg/m2 in this subgroup. In addition, 10 patients (13.70%) developed diarrhea of grade 3/4 and 20 cases (27.4%) developed paralytic ileus of any grade, which may be related to the neuropathy toxicity of btz too. Correlation analysis showed that only voriconazole combination was significantly correlated with PN development (p<0.0001). However, any other factors, including age, sex, the percentage of plasma cells in bone marrow, the level of M-protein, IL-6, TNF-α, β2-MG, ALB, calcium, the type of M-protein, etc, were all without correlation with the development of PN. Conclusions Voriconazole combination significantly increased the risk and the grade of PN in patients treated with btz-based chemotherapy. If this combination can't be avoided, patients should be observed more closely or btz dosage should be decreased earlier. Disclosures No relevant conflicts of interest to declare.

Updated results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8527-8527 ◽  
Author(s):  
R. Amaravadi ◽  
L. M. Schuchter ◽  
D. F. McDermott ◽  
A. Kramer ◽  
L. Giles ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Prior History ◽  
Prior Therapy ◽  
Optimal Dosing ◽  
Significant Difference ◽  
Grade 3 ◽  
Induced Apoptosis

8527 Background: The preliminary results for 90 patients (pt) on this 4-arm phase II trial testing sorafenib (SO), an oral Raf kinase/VEGFR2 inhibitor, and temozolomide (TEM) in pt with metastatic melanoma (MM) were presented in 2006. Since then 88% of target accrual is completed and the study is open at a second institution. The primary objective of this study is to estimate the duration of progression- free survival (PFS). Secondary objectives are to determine the optimal dosing of TEM, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition, and apoptosis. Methods: Pt with MM and ECOG PS<2 are eligible. Prior therapy is allowed. Target accrual is 167 pt in 1 stage. All pt receive SO 400 mg po bid continuously. After 1 week of SO alone, pt without brain metastasis or prior TEM (A+B) are randomized to receive either extended dosing (ED): TEM 75 mg/m2 po qd for 6/8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m2 po qd for days1–5/28 (Arm B). Pt with prior TEM are treated with ED (Arm C) and pt with brain metastasis without prior TEM are treated with STD (Arm D). Responses are assessed using RECIST. Results: Accrual is complete for arms A and B. Results for 147 pt were evaluated ( Table ). SO + TEM resulted in a 19% overall response rate (ORR) [95% CI 11–30%] for pt on arms A+B. In this group, 3/78 pt (4%) developed CNS metastases while on study. Pt on arm D had a 17 % ORR [95% CI 7–34%]. Common grade 3 toxicities were hand-foot syndrome (14%), rash (9%), nausea (9%), and diarrhea (5%). Grade 3 lymphopenia was more common in arm A v. B (43% v. 16%, p=0.01). No significant difference in PFS was found between pt with WT v. mutant BRAF (n=33). Therapy-induced apoptosis was found in 8/9 serial biopsies. Analysis of MAPK phosphorylation in serial biopsies is planned. Conclusions: Updated results confirm the encouraging antitumor activity and tolerability of SO + TEM in pt with MM without a prior history of TEM. No significant financial relationships to disclose. [Table: see text]

A randomized phase II clinical trial of gemcitabine, oxaliplatin, erlotinib combination chemotherapy versus gemcitabine and erlotinib in previously untreated patients with locally advanced or metastatic pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 344-344 ◽  
Author(s):  
Sung Hee Lim ◽  
Jina Yun ◽  
Min-Young Lee ◽  
Han Jo Kim ◽  
Kyoung Ha Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Overall Response ◽  
Significant Difference ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

344 Background: Erlotinib is the only targeted agent in combination with gemcitabine showing significantly improved outcomes in pancreatic cancer. Although combining platinum agent with gemcitabine has not provided clear survival benefit over gemcitabine alone, gemcitabine plus platinum resulted in improved response rate and progression-free survival (PFS). We tried to evaluate whether the addition of oxaliplatin to gemcitabine/erlotinib confers a clinical benefit to patients with locally advanced or metastatic pancreatic cancer. Methods: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T (gemcitabine 1000mg/m2 IV and oxaliplatin 50mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks) or GT (gemcitabine 1000mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks). The primary endpoint was overall response and secondary endpoints included PFS, overall survival (OS) and toxicity. Results: Between May 2013 and April 2016, 65 patients were randomly assigned to treatment group (33 in GEMOX-T arm, 32 in GT arm). The median age of all patients was 61 years (range, 41-76) and about 80% of patients had metastatic disease. The overall response rate was 18.2 % in GEMOX-T arm and 6.2% in GT arm ( P = 0.051). The disease control rate was significantly superior in GEMOX-T arm compared to GT arm (72.7% vs. 43.8%, P = 0.019), with 1 patient in GEMOX-T group continuing the treatment with stable disease. After a median follow up of 19.7 months, there was significant difference in PFS: the median PFS were 3.9 months for GEMOX-T arm and 1.4 months for GT arm (Hazard ratio: 0.58, 95% CI 0.35-0.96, P = 0.037). However, it did not translate to improvement of OS (median OS; 6.2 m for GEMOX-T arm, 5.1 m for GT arm, P = 0.118). The most common grade ≥ 3 hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). Conclusions: The addition of oxaliplatin to 1st line gemcitabine/erlotinib regimen demonstrated higher response rate and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

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