Tumor response in the CLARINET study of lanreotide depot vs. placebo in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 434-434 ◽  
Author(s):  
Alexandria T. Phan ◽  
Arvind Dasari ◽  
Nilani Liyanage ◽  
David Cox ◽  
Susan Pitman Lowenthal ◽  
...  
Keyword(s):  
Tumor Response ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Well Differentiated ◽  
Long Acting ◽  
Favorable Safety

434 Background: In the CLARINET study, significant improvement in progression-free survival (primary endpoint) was reported in patients (pts) treated with lanreotide depot (LAN), a long-acting somatostatin analog, for moderately- or well-differentiated, nonfunctioning, locally advanced or metastatic GEP-NETs. A favorable safety profile was also observed. This retrospective analysis presents tumor response from CLARINET. Methods: Pts were randomized to LAN 120 mg (n=101) or PBO (n=103) once every 28 days for 96 weeks. Tumor response was evaluated centrally using RECIST version 1.0. Pts’ tumors were measured by sum of the longest diameter (SLD) of target lesions (TLs). Change was calculated for each pt’s SLD from baseline to last available post-baseline assessment. Tumor response was classified as complete response (CR): disappearance of all TLs and non-target lesions (NTLs) and no new lesions; partial response (PR): ≥30% decrease in SDL and no progressive disease (PD); stable disease (SD): not meeting criteria for CR/PR or PD; PD: ≥20% increase in SLD from baseline or nadir, unequivocal progression of NTLs or appearance of new lesions. The remaining pts were not evaluable (NE) for response. Results: 101 pts treated with LAN and 103 pts treated with PBO were assessed for tumor response. Among pts receiving LAN, 64% (65/101) demonstrated SD compared to 43% (44/103) of pts receiving PBO (Table). An additional 2 pts in the LAN group achieved a PR. Similar trends were observed in pts with pancreas and midgut origin tumors. Conclusions: A clinical benefit (defined as CR+PR+SD) of 66% (67/101) was observed with single agent LAN vs 43% (44/103) with PBO in the CLARINET population, further supporting the clinical efficacy of LAN. Clinical trial information: NCT00353496. [Table: see text]

Effect of lanreotide depot (LAN) on 5-hydroxyindoleacetic acid (5HIAA) and chromogranin A (CgA) in gastroenteropancreatic neuroendocrine (GEP NET) tumors: Correlation with tumor response and progression-free survival (PFS) from the phase III CLARINET study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4095-4095
Author(s):  
Alexandria T. Phan ◽  
Edward M. Wolin ◽  
Nilani Liyanage ◽  
Beloo Mirakhur ◽  
Susan W. Pitman Lowenthal ◽  
...  
Keyword(s):  
Tumor Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Upper Limit ◽  
Hydroxyindoleacetic Acid ◽  
Well Differentiated ◽  
Clinical Trial Information ◽  
Radiologic Progression

4095 Background: 5HIAA or CgA are biomarkers in some GEP NETs. We present posthoc analyses using prospectively collected urinary 5HIAA and serum CgA data from CLARINET. Methods: Adults with moderately or well differentiated, nonfunctioning (no symptoms of carcinoid syndrome), locally advanced or metastatic GEP NETs were randomized to LAN 120mg or placebo (PBO) every 4 weeks (wks) for 96 wks. Tumor response evaluated centrally (RECIST 1.0) and PFS were assessed by treatment. Biochemical response was defined as baseline > upper limit of normal (ULN, 41.6µmol/d 5HIAA; 98.1µg/L CgA) and ≥50% decrease from baseline to ≤ULN value on study. CgA analyses excluded gastrinoma patients (pts). Results: 48% (82/171) (45LAN; 37PBO) and 66% (129/195) (65LAN, 64PBO) of pts had > ULN baseline 5HIAA and CgA. In those pts with no radiologic progression, significantly greater reductions in 5HIAA (Table) and CgA were observed in LAN vs PBO pts at all assessments (all P< 0.05). PFS was significantly prolonged in LAN 5HIAA responders vs nonresponders (median not reached vs 22.1 months, P= 0.0076) but was not significantly different in PBO 5HIAA responders vs nonresponders. There were no significant differences in PFS by CgA response (responders vs nonresponders) in either LAN or PBO pts. Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496. [Table: see text]

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

scholarly journals 177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

2021 ◽  
pp. 1167-1175
Author(s):  
Swayamjeet Satapathy ◽  
Bhagwant R. Mittal ◽  
Ashwani Sood ◽  
Apurva Sood ◽  
Rakesh Kapoor ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Octreotide Lar ◽  
Treatment Naïve ◽  
Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

Results of a phase 2 study of bortezomib in patients with relapsed or refractory indolent lymphoma

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Nicholas Di Bella ◽  
Raymond Taetle ◽  
Kathryn Kolibaba ◽  
Thomas Boyd ◽  
Robert Raju ◽  
...  
Keyword(s):  
Median Time ◽  
Single Agent ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Low Grade ◽  
Free Survival ◽  
Ann Arbor ◽  
Duration Of Response ◽  
Unconfirmed Complete Response

Abstract This study evaluated the efficacy and safety of single-agent bortezomib in indolent B-cell lymphoma that had relapsed from or was refractory to rituximab. Sixty patients enrolled: 59 were treated with bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 for up to eight 21-day cycles; responders could receive 4 additional cycles; maintenance was optional. Fifty-three evaluable patients completed more than 2 cycles. The median age was 70 years, 53% female, Ann Arbor stage III-IIIE (28%) and IV (65%); 43 patients (72%) had more than 2 prior regimens; and 6 patients went on to maintenance. Overall responses are as follows: 1 complete response (1.9%), 3 unconfirmed complete response (5.7%), 3 partial response (5.7%), 34 stable disease (64.2%), and 12 progressive disease (22.6%). Median time to response = 2.2 months (range, 1.2-5.3 months); duration of response = 7.9 months (2.8-21.3 months); 1-year survival was 73% and 2-year survival was 58%; median survival = 27.7 months (range, 1.4-30.9 months); median progression-free survival = 5.1 months (range, 0.2-27.7 months), median time to progression = 5.1 months (range, 0.2-27.7 months), and median event-free survival = 1.8 months (range, 0.2-27.7 months). Treatment-related grade 3 or 4 adverse events included: thrombocytopenia (20%), fatigue (10%), neutropenia (8.5%), and neuropathy and diarrhea (6.8% each). This study demonstrates that bortezomib has modest activity against marginal zone and follicular lymphoma; it has the potential for combination with other agents in low-grade lymphomas. Maintenance therapy should be explored further.

The combination of intravenous bevacizumab and metronomic oral cyclophosphamide for recurrent platinum-resistant ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Emma L. Barber ◽  
Nikki Lynn Neubauer ◽  
Emese Zsiros ◽  
Julian C. Schink
Keyword(s):  
Overall Survival ◽  
Ovarian Carcinoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Ca 125 ◽  
Oral Cyclophosphamide ◽  
Free Survival ◽  
Platinum Resistant

5039 Background: This study was undertaken to determine the progression free survival and overall survival in heavily pre-treated patients with recurrent ovarian carcinoma treated with bevacizumab and metronomic oral cyclophosphamide. Methods: An IRB-approved retrospective review was performed for all patients with recurrent ovarian, fallopian tube or primary peritoneal carcinomas treated with intravenous bevacizumab 10mg/kg every 14 days and oral cyclophosphamide 50mg daily between January 2006 and December 2010. Response to treatment was determined by change in disease status according to RECIST criteria and/or CA-125 levels. Results: Sixty-six eligible patients were identified with a median age of 58 years. Fifty-five patients (83%) originally had optimal cytoreduction and all were platinum resistant. Median time from diagnosis to beginning bevacizumab and cyclophosphamide was 36 months. Median number of prior chemotherapy treatments was 7.5 (range 3-16). Eight patients (12.1%) had side effects which required discontinuing bevacizumab and cyclophosphamide, most common were hypertension, proteinuria, and fatigue. There was one bowel perforation (1.5%). A complete response was noted in 7 patients (10.6%), partial response was seen in 21 patients (31.8%) with an overall response rate of 42.4%. Fifteen patients (22.7%) had stable disease and 23 (34.8%) had disease progression. Median progression free survival (PFS) for responders was 5 months (range 2-14) and 11 months (range 4-14) for those with a complete response. Median overall survival (OS) from start of bevacizumab and cyclophosphamide for responders was 20 months (range 2-56) and 9 months (range 1-51) for nonresponders. Conclusions: Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy regimen in heavily pre-treated patients with recurrent ovarian carcinoma which significantly improves PFS and OS in responders. Response rates were significantly better than the rates we have reported in this same group of patients receiving topotecan (22%) or liposomal doxorubicin (25%) and were superior to reported rates for single agent bevacizumab (18%) in patients with only 2-3 prior regimens.

EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4681-TPS4681 ◽  
Author(s):  
Ian D. Davis ◽  
Val Gebski ◽  
Mark D. Chatfield ◽  
Peter S. Grimison ◽  
George Kannourakis ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Prognostic Score ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).

Efficacy of abemaciclib (abema) after palbociclib (palbo) in patients (pts) with metastatic breast cancer (MBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12521-e12521 ◽  
Author(s):  
Veronica Mariotti ◽  
Hung T. Khong ◽  
Hatem Hussein Soliman ◽  
Ricardo L Costa ◽  
Shanel Fisher ◽  
...  
Keyword(s):  
Endocrine Therapy ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Disease Status ◽  
Complete Response ◽  
Cross Resistance ◽  
Tumor Characteristics ◽  
Limited Data ◽  
Free Survival

e12521 Background: CDK 4/6 inhibitors (Abema and Palbo) have shown efficacy in patients with HR+/HER2- MBC. Abema is distinct from other CDK 4/6 inhibitors and was approved after the approval of Palbo. There is limited data on sequential use or cross resistance. The aim of this study was to analyze the response to Abema based therapy in MBC pts with prior exposure to Palbo. Methods: We queried our EMR database for pts who received Abema from 9/2017-9/2018 after having received prior Palbo. Under IRB approved protocol we retrospectively collected demographics, tumor characteristics, disease status, toxicities and survival. Results: 23 female pts were identified. Four patients discontinued Palbo due to toxicities: two of them remained on Abema for 8 months and the other 2 discontinued Abema due to toxicities. The remaining 19 pts (median age 57 years, range 39-76) received a mean of 5.6 prior therapies (range (1-11) including Palbo in combination with endocrine therapy (fulvestrant 9 in pts and Aromatase inhibitors (AI) in 10 pts) at the time of Abema based therapy. 73.6% had visceral involvement including brain metastasis in 26%. The median progression-free survival (PFS) of Palbo in combination with endocrine therapy was 8 months (range 2.3-14.3). Abema was given in combination with endocrine therapy in 15 pts (9 pts fulvestrant and 6 pts AI) and 4 pts received it as a single agent. The median PFS of Abema based therapy was 7.0 months (range 1.8-12.1). Four pts (21%) had a longer PFS on Abema compared to prior Palbo PFS (table). Abema was discontinued due to toxicities in 15.7%. No partial or complete response was observed but 33% had stable disease. Conclusions: Abema showed response in a significant number of pts previously exposed to Palbo and heavily treated with multiple lines of chemotherapy for widespread metastatic disease. Prospective studies are warranted to better assess the response to Abema after exposure to CDK4/6 inhibitors. [Table: see text]

scholarly journals Self-Administration of Long-Acting Somatostatin Analogues in NET Patients—Does It Affect the Clinical Outcome?

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1287
Author(s):  
Anna Sowa-Staszczak ◽  
Marta Opalińska ◽  
Anna Kurzyńska ◽  
Karolina Morawiec-Sławek ◽  
Aleksandra Gilis-Januszewska ◽  
...  
Keyword(s):  
Medical Staff ◽  
Somatostatin Receptor ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Self Administration ◽  
Good Expression ◽  
Well Differentiated ◽  
Long Acting

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.

Maintenance chemotherapy with pemetrexed in epiteliomorfe malignant pleural mesothelioma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18545-e18545
Author(s):  
Angelo Nacci ◽  
Claudio Lotesoriere ◽  
Michele Montrone ◽  
Salvatore Pisconti ◽  
Laura Orlando ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Induction Therapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pleural Mesothelioma ◽  
Maintenance Chemotherapy ◽  
Free Survival ◽  
Vitamin B12 Supplementation

e18545 Background: Maintenance chemotherapy with pemetrexed is not the standard treatment of choice in patients with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM). We would assess the safety and efficacy of a treatment with pemetrexed until progression disease after 4 or 6 cycles of induction therapy with or without platin. Methods: From July 2008 to September 2012, 21 patients (18 males and 3 females with a median age of 67 years range 58-84) with locally advanced or metastatic epiteliomorfe malignant pleural mesothelioma (EMPM) were enrolled. In all patients histology was epiteliomorfe malignant mesothelioma. Only 15 patients (71,4%) had a PS 0 whereas 6 (28,6%) had a PS 1. All patients received an induction therapy with or without platin. Each patient received an average of 5,6 cycles of induction chemotherapy. Then all patients received a maintenance chemotherapy with pemetrexed 500 mg/mq intavenously over 10 minutes every 3 weeks. Each patient received an average of 7,3 cycles of maintenance chemotherapy. All patients received folic acid and vitamin B12 supplementation to improve safety. Results: At the time of analysis all patients were evaluable for response. Fourteen patients (66,6 %) had a partial response and two of these underwent surgery and obtained a complete response. Six patients (28,5%) had a stable disease. The median overall survival was 13 months, while median progression-free survival was 11 months. Grade 2-3 of WHO haematological toxicities (anemia and neutropenia) occurred in 4 patient (19%). We also observed grade 2-3 of WHO gastrointestinal toxicities (diarrhea, nausea and vomiting) in 2 patient (9.5%). Grade 2 of lack of appetite and asthenia occurred in 3 patients (14.3%). Conclusions: Our data show that a maintenance chemotherapy with pemetrexed in EMPM resulted in a moderate overall survival (13 months). These results indicate that patients with EMPM could benefit from a maintenance treatment with pemetrexed.

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 228-228
Author(s):  
Hope Elizabeth Uronis ◽  
Christel Rushing ◽  
Gerard C. Blobe ◽  
Shiaowen David Hsu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
First Line ◽  
Tumor Biopsy ◽  
Gastroesophageal Junction Adenocarcinoma

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m2 every three weeks and oral C 850mg/m2 twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

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