Lenalidomide with Low or Intermediate Dose Dexamethasone in Patients with Relapsed or Refractory Myeloma

Abstract Abstract 4028 Lenalidomide is an immunomodulatory drug with significant efficacy in relapsed and refractory multiple myeloma (MM) in combination with high or intermediate dose dexamethasone (RD). Previous studies in newly diagnosed patients (pts) showed that the combination of lenalidomide plus low dose dexamethasone (Rd) is associated with better overall survival (OS) and lower toxicity. However, there are no data comparing different dose of dexamethasone with lenalidomide in pts with relapsed or refractory myeloma. To address this issue we analyzed, retrospectively, 102 consecutive pts with relapsed or refractory MM, treated in a single center (Department of Clinical Therapeutics, University of Athens, Greece), who received lenalidomide with dexamethasone: 70 patients received lenalidomide and dexamethasone at a dose 40 mg PO, on days 1–4 and 15–18 for the first 4 cycles and only on days 1–4 thereafter (intermediate dose; group RD) and 32 pts who received lenalidomide and low dose dexamethasone (40 mg PO weekly; group Rd). Lenalidomide was administered on days 1–21 according to creatinine clearance (CrCl): 25mg/day for CrCl >50 ml/min, 10 mg/day for CrCl 30–50 ml/min, 15 mg every other day for CrCl 15–29 ml/min and for pts on dialysis 5 mg, once daily. RD and Rd were repeated every 28 days till disease progression or unacceptable toxicity. All pts received DVT prophylaxis with aspirin 100 mg/day except 18 pts (18%) who were already on coumadin or LMWH for other indications (atrial fibrillation, previous DVT, etc). The median age of the pts was 67 years for RD and 69 years for Rd (p=0.36). There were no significant differences regarding the presence of specific cytogenetic abnormalities or high risk cytogenetics (p>0.3 for all comparisons). Patients in group RD were more heavily pretreated and had more often exposed to thalidomide (69% vs. 43%, p=0.013) or bortezomib (76% vs. 63%, p=0.1) and had more often thalidomide resistance (43% vs. 10%, p=0.001) or bortezomib resistance (46% vs. 20%, p=0.014). The number of prior therapies in group RD was 2 (range: 1–6) vs. 1 (range: 1–3) in group Rd (p=0.007), while 60% in RD vs. 30% in Rd were refractory to last line of therapy (p=0.006). Pts in RD have received a median of 10 cycles (range: 1–44 cycles) and only 2 pts are still receiving therapy, while pts in Rd have received a median of 5 (range: 1–17) cycles but 21 (70%) continue to receive treatment. The median follow-up was 18 months (range: 1–58 months) for RD and 7.6 months (range: 1.9–23.6 months) for Rd. Responses, according to IMWG criteria, were not different among the two groups: in RD, CR (26%), PR (36%), SD (26%), PD (12%) and in Rd, CR (13%), PR (53%), SD (27%) and PD (7%). At least PR was observed in 32% of pts in RD and in 66% in Rd (p=0.45) of thalidomide-refractory pts, and in 45% in RD and 33% in group Rd (p=0.72) of bortezomib-refractory pts. The median progression-free survival (PFS) was 10 months (range: 1–55 months) for RD and has not been reached for Rd, but the 6-month PFS rate was 84% (p=0.003). The median time to next treatment was 11 months (range: 0.9–53 months) for RD and has not been reached for Rd. The OS was 18 months (range: 0.9–58 months) for RD and has not been reached for Rd, but the 1-year probability for OS was 81% (p=0.27). After adjustment for prior thalidomide and/or bortezomib resistance, disease refractory to last line of therapy and number of prior therapies, there was no difference for RD vs. Rd for OS (HR: 1.7, 95% CI 0.572–5, p=0.338) but Rd was associated with better PFS than RD (HR: 0.36, 95% CI 0.14–0.95, p=0.038). We also evaluated the effect of treatment on renal impairment reversal. Twenty nine pts (40%) in group RD and 7 pts (23%) in group Rd had an eGFR, calculated by the MDRD formula, of <60 ml/min. Seven patients (25%) from group RD and none from group Rd achieved renal response (p=0.199), according to the IMWG criteria. More patients treated with RD developed grade ≥3 neutropenia (23% vs. 3%) and fatigue ≥grade 3 (15% vs. 3%); 3 pts from group RD developed thrombosis (2 patients DVT and one pulmonary embolism) vs. none with Rd. Other toxicities occurred with similar frequency between RD and Rd. This is the first analysis, which compared the role of intermediate and low dose dexamethasone with lenalidomide in pts with relapsed or refractory myeloma. Our data indicate that Rd is probably as effective as RD, while it may be better tolerated. Updated results regarding OS and PFS as well as renal recovery will be presented at the meeting. Disclosures: Dimopoulos: Celgene: Honoraria. Terpos:Celgene: Honoraria.

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FAS and Subsequent Therapies in Pancreatic Neuroendocrine Tumors

Neuroendocrinology ◽

10.1159/000514339 ◽

2021 ◽

Author(s):

Jane E. Rogers ◽

Michael Lam ◽

Daniel M. Halperin ◽

Cecile G. Dagohoy ◽

James C. Yao ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Cox Regression ◽

Progression Free Survival ◽

Pancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Prior Therapy ◽

Well Differentiated ◽

Grade 3 ◽

Line Of Therapy

We evaluated outcomes of treatment with 5-fluorouracil (5-FU), doxorubicin, and streptozocin (FAS) in well-differentiated pancreatic neuroendocrine tumors (PanNETs) and its impact on subsequent therapy (everolimus or temozolomide). Advanced PanNET patients treated at our center from 1992 to 2013 were retrospectively reviewed. Patients received bolus 5-FU (400 mg/m2), streptozocin (400 mg/m2) (both IV, days 1-5) and doxorubicin (40 mg/m2 IV, day 1) every 28 days. Overall response rate (ORR) was assessed using RECIST version 1.1. Of 243 eligible patients, 220 were evaluable for ORR, progression-free survival (PFS), and toxicity. Most (90%) had metastatic, nonfunctional PanNETs; 14% had prior therapy. ORR to FAS was 41% (95% confidence interval [CI]: 36-48%). Median follow-up was 61 months. Median PFS was 20 (95% CI: 15-23) months; median overall survival (OS) was 63 (95% CI: 60-71) months. Cox regression analyses suggested improvement with first-line vs subsequent lines of FAS therapy. Main adverse events ≥ grade 3 were neutropenia (10%) and nausea/vomiting (5.5%). Dose reductions were required in 32% of patients. Post-FAS everolimus (n=108; 68% second line) had a median PFS of 10 (95% CI: 8-14) months. Post-FAS temozolomide (n=60; 53% > fourth line) had an ORR of 13% and median PFS of 5.2 (95% CI: 4-12) months. In this largest reported cohort of PanNETs treated with chemotherapy, FAS demonstrated activity without significant safety concerns. FAS did not appear to affect subsequent PFS with everolimus; this sequence is being evaluated prospectively. Responses were noted with subsequent temozolomide-based regimens although PFS was possibly limited by line of therapy.

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Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e17552 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e17552-e17552

Author(s):

Rodrigo Sanchez-Bayona ◽

Pablo Tolosa ◽

Ana Sanchez de Torre ◽

Alicia Castelo ◽

Elsa Bernal-Hertfelder ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Ovarian Carcinoma ◽

Progression Free Survival ◽

High Grade ◽

Efficacy And Safety ◽

Free Survival ◽

Serous Ovarian Carcinoma ◽

Platinum Resistant ◽

Heavily Pretreated ◽

Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

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Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.20.02259 ◽

2020 ◽

pp. JCO.20.02259

Author(s):

Paul G. Richardson ◽

Albert Oriol ◽

Alessandra Larocca ◽

Joan Bladé ◽

Michele Cavo ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Free Survival ◽

Duration Of Response ◽

Heavily Pretreated ◽

Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

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Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽

10.1159/000440942 ◽

2015 ◽

Vol 61 (1) ◽

pp. 23-31 ◽

Cited By ~ 4

Author(s):

Noriyoshi Miura ◽

Nozomu Tanji ◽

Yutaka Yanagihara ◽

Terutaka Noda ◽

Seiji Asai ◽

...

Keyword(s):

Prostate Cancer ◽

Low Dose ◽

Specific Antigen ◽

Progression Free Survival ◽

Hematological Toxicity ◽

Castration Resistant Prostate Cancer ◽

Gastric Bleeding ◽

Castration Resistant ◽

Analgesic Agents ◽

Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

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A pilot study of apatinib reversing paclitaxel resistance in heavily pretreated advanced gastric cancer (AGC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.89 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 89-89

Author(s):

Rongbo Lin ◽

Shen Zhao ◽

Hui Li ◽

Jie Liu ◽

Nanfeng Fan

Keyword(s):

Disease Progression ◽

Promising Result ◽

Performance Status ◽

Early Death ◽

Progression Free Survival ◽

Chemotherapeutic Agents ◽

Paclitaxel Resistance ◽

Heavily Pretreated ◽

Grade 3

89 Background: In vitro or vivo, apatinib can reverse ABC-mediated multidrug resistance not only by inhibiting their transport function, but also by downregulating ABC expression. Methods: The patients with advanced gastric adenocarcinoma were resistant to paclitaxel-containing regimen (disease progression during or within 3 months after chemotherapy) and had measurable lesions received apatinib 850 mg, po, qd combined with paclitaxel alone (80 mg/m2 d1, d8, and d15, repeated 4-weekly) or POF (reported in 2007, 2008, 2009, 2010 ASCO, paclitaxel 135 mg/m2, oxaliplatin 85 mg/m2, and leucovorin 400 mg/m2, d1; 5-FU 2400 mg/m2 for 46h, repeat 2-weekly). The choice of regimen was left to clinician discretion in term of performance status and whether the agent that will be given has been resistant. Results: From 14th August 2015 to 1st March 2016, seven patients were eligible. The median age was 49 years (range, 43 to 67 years), 5 were males and 2 were females. The prior chemotherapeutic agents were summarized in table. Four patients had disease progression during apatinib. Two PRs, four SDs (unconfirmed), and one early death were observed. At a median follow-up of 238 days, the median progression-free survival was 124 days, the median survival was 194 days (range, 33 to 398+ days). Grade 3 to 4 neutropenia, anaemia, hypertension, fatigue, stomatitis was one patient respectively. No treatment-related death occurred. Conclusions: This study showed promising result that apatinib reverses paclitaxel resistance in heavily pretreated AGC. Clinical trial information: NCT02697838. [Table: see text]

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Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4040 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4040-4040 ◽

Cited By ~ 5

Author(s):

Heinz-Josef Lenz ◽

Sara Lonardi ◽

Vittorina Zagonel ◽

Eric Van Cutsem ◽

M. Luisa Limon ◽

...

Keyword(s):

Clinical Benefit ◽

Low Dose ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

Free Survival ◽

Duration Of Response ◽

Therapy Option ◽

Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

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Low-dose cisplatin administration through the superficial temporal artery combined with definitive radiotherapy for maxillary sinus squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18562 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18562-e18562

Author(s):

Tatsuo Masubuchi ◽

Yosuke Kitani ◽

Chihiro Fushimi ◽

Daisuke Kawakita ◽

Hideaki Takahashi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Low Dose ◽

Superficial Temporal Artery ◽

Progression Free Survival ◽

Temporal Artery ◽

Efficacy And Safety ◽

Free Survival ◽

Grade 3

e18562 Background: Although patients with locoregional advanced maxillary sinus squamous cell carcinoma (MSSCC) are often treated with surgery followed by postoperative radiotherapy (RT), the cosmetic and functional outcomes are unsatisfactory. Moreover, the efficacy and safety of intra-arterial chemoradiotherapy are controversial. Methods: In this study, we investigated the efficacy and safety of low-dose cisplatin administration through the superficial temporal artery (STA) combined with definitive RT in patients with MSSCC. Between January 2009 and December 2018, 57 patients were administered weekly intra-arterial infusions of cisplatin (30–50 mg/m2/5h) through the STA with simultaneous intravenous infusions of sodium thiosulfate. Overall response rate (ORR), local progression-free survival (LFS), maxillectomy-free survival (MFS), progression-free survival (PFS), overall survival (OS), and safety were evaluated retrospectively. The impact of clinical factors on survival was investigated using the Cox proportional hazard models. Results: The median follow-up time was 44 months (range, 10–80 months). There were 4, 26, 23, and 4 patients with cT2, cT3, cT4a, and cT4b, respectively. All patients completed the planned treatment except for one patient who discontinued owing to facial palsy. The ORR was 98% with 51 and 5 patients having complete and partial responses, respectively. The 3-year LFS, PFS, and OS were 74%, 63%, and 81%, respectively for all patients and 100%, 81%, and 94%, respectively for 22 patients received 70 Gy irradiation. Notably, the 3-year MFS was 95% for all patients and 100% in patients received 70 Gy RT. The most common grade 3 or more toxic event was oral mucositis (22.8%). Additionally, 4 (7.0%) patients had catheter-related infections. Late grade 3 or more adverse events included optic nerve disorder (8.8%), osteonecrosis (7.0%), encephalopathy (1.8%), and increased creatinine levels (1.8%). Salvage surgery including hard palate resection and orbital exenteration were performed in 2 and 1 patients, respectively. No clinical factor was correlated with survival outcomes in our study cohort. Conclusions: Low-dose cisplatin through STA combined with RT, especially 70 Gy RT, was associated with promising tumor response, high organ preservation rate, and tolerable adverse events in MSSCC patients. Further prospective studies are warranted to compare these outcomes with primary surgery.

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Avelumab in patients with previously treated metastatic melanoma: Phase 1b results from the JAVELIN Solid Tumor trial.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.191 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 191-191 ◽

Cited By ~ 2

Author(s):

Ulrich Keilholz ◽

Janice M. Mehnert ◽

Sebastian Bauer ◽

Hugues Pierre Bourgeois ◽

Manish R. Patel ◽

...

Keyword(s):

Metastatic Melanoma ◽

Objective Response ◽

Progression Free Survival ◽

Complete Response ◽

Duration Of Response ◽

Previously Treated ◽

Phase 1B ◽

Advanced Urothelial Carcinoma ◽

Grade 3 ◽

Line Of Therapy

191 Background: Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody that is approved for the treatment of metastatic Merkel cell carcinoma (US and EU) and advanced urothelial carcinoma progressed on platinum therapy (US). Here, we report phase 1b data for avelumab in a cohort of patients (pts) with previously treated metastatic melanoma. Methods: Pts with unresectable stage IIIC or IV melanoma progressed after ≥1 line of therapy for metastatic disease received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs; NCI CTCAE v4.0). Results: As of Dec 31, 2016, 51 pts were treated and followed for a median of 24.2 mo (range 16.1–31.5). Median age was 64 y (range 31–84). Site of primary tumor was cutaneous (n = 28, 54.9%), ocular (n = 16, 31.4%), mucosal (n = 2, 3.9%), or unknown (n = 5, 9.8%). Pts had received a median of 2 prior lines of therapy for advanced disease (range 0–4), including ipilimumab (n = 26, 51.0%). Confirmed ORR was 21.6% (95% CI 11.3–35.3), with complete response in 7.8% and partial response in 13.7%. In pts with cutaneous melanoma, ORR was 28.6% (95% CI 13.2–48.7). There were no objective responses in pts with ocular melanoma; however, 7 pts (43.8%) had stable disease. In pts with ≤1 (n = 25), 2 (n = 17), or ≥3 (n = 9) prior lines, ORR was 36.0% (95% CI 18.0–57.5), 11.8% (95% CI 1.5–36.4), and 0% (95% CI 0–33.6), respectively. Antitumor activity by PD-L1 status will be presented. Median duration of response was not estimable (NE) (95% CI 2.6 mo–NE). Median PFS was 3.1 mo (95% CI 1.4–6.3) and the 6-mo PFS rate was 39.2% (95% CI 25.2–52.9). Median OS was 18.5 mo (95% CI 9.3–NE) and the 12-mo OS rate was 62.3% (95% CI 46.9–74.4). 39 pts (76.5%) had a treatment-related (TR)AE, most commonly infusion-related reaction (25.5%), fatigue (17.6%), and chills (11.8%). 4 pts (7.8%) had a grade ≥3 TRAE. 5 pts (9.8%) had an immune-related AE; all were grade 1/2. No treatment-related deaths occurred. Conclusions: Avelumab showed durable responses, promising survival outcomes, and an acceptable safety profile in pts with previously treated metastatic melanoma. Clinical trial information: NCT01772004.

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Combined Treatment of Bortezomib, Continuous Low-Dose Cyclophosphamide and Dexamethasone Followed By One Year of Maintenance Treatment for Refractory or Relapsed Multiple Myeloma Patients: A Prospective Phase II Study

Blood ◽

10.1182/blood.v124.21.4733.4733 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4733-4733

Author(s):

Esther GM Waal de ◽

Linda Munck de ◽

Gerhard Woolthuis ◽

Annet velden Van Der ◽

Yvonne Tromp ◽

...

Keyword(s):

Overall Survival ◽

Maintenance Therapy ◽

Research Funding ◽

Low Dose ◽

Progression Free Survival ◽

Free Survival ◽

First Relapse ◽

Grade 3 ◽

One Year

Abstract Introduction: Combination therapy for longer periods but at low dose, also called metronomic scheduling, might be an effective manner to treat patients with relapsing myeloma. In particular if the used agents attack the malignant clone in an alternative manner. Therefore we used the combination of bortezomib, dexametasone and daily low dose of oral cyclophosphamide as an induction regimen followed by one year of maintenance therapy consisting of bortezomib and cyclophosphamide. Methods: Relapsing myeloma patients, bortezomib naïve, were treated with three cycles of 1.3 mg/m2 bortezomib at day 1, 4, 8 and 11, cyclophosphamide 50 mg daily, and 20 mg dexamethasone at day 1, 2, 4, 5, 8, 9, 11 and 12 followed by three cycles of bortezomib 1.6 mg/m2 (day 1, 8, 15 and 2), cyclophosphamide (50 mg) daily and dexamethasone (20 mg) at day 1, 2, 8, 9, 15, 16, 22 and 23. Maintenance therapy consisting of bortezomib 1.3 mg/m2 every two weeks and daily dose of 50 mg cyclophosphamide for one year was applied to patients in partial or complete remission. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression free and overall survival. Results: 59 patients with relapsing multiple myeloma were included of whom 69% were in first relapse (Table 1). The upfront treatment consisted mainly of thalidomide-based and vincristine-based chemotherapy and 40% of the patients have been treated with an autologous stem cell transplantation. All 6 cycles of induction chemotherapy could be given in 49% of the patients. Premature discontinuation before starting maintenance therapy was due to toxicity (31%), progressive disease (7%), death (7%) or other reasons (6%). Myelosuppression was the most common side effect with WHO grade 3-4 in 31% of the patients. Neuropathy grade 3-4 was observed in 16% of patients, partially due to the fact that bortezomib was given intravenously during the first 2 yrs of the protocol which included 76% of the patients. Maintenance therapy was started in 47% of the patients with a median duration of 7.3 months (range 0.36.-13.4). Grade 3-4 toxicity was observed in 25% of the patients including infections (n=3) and myelosuppression (n=3) which did not resulted in discontinuation of therapy. Median follow up time was 29 months with an overall response of 62%, and a very good partial response (VGPR), complete remission (CR) in 21% and 7% of the patients respectively. During the maintenance phase an improvement in responsiveness was observed in 25% of the patients. The CR rate increased with 9% to a total of 16%. VGPR rate was 20% and 16% of the patient had a PR. At end of the maintenance therapy 50% of patients started with maintenance had stable disease. The median progression free survival (PFS) was 17.2 months (range 0.13 – 43.5) as depicted in figure 1. and the median overall survival was 21.6 months (range 0.46-54.4, figure 2). During follow up 33 % of the patients died due to progression of MM. Conclusion: The present study demonstrates that combination therapy with bortezomib, continuous low dose cyclophosphamide and dexamethasone is an effective and manageable regimen. Adding a year of maintenance was feasible with limited side effects and an increase in CR rate. Table 1: patient characteristics Patients (%) Age, mean (min,max) 69 (46-86) Sex Male 56 Female 44 Relapse number First relapse 75 Second relapse 20 Third relapse 5 Performance status 0 65 1 29 2 5 M-protein heavy chain IgA 18 IgG 65 Light chain disease 18 Polyneuropathy No 61 Yes 39 Figure 1: Progression free survival Figure 1:. Progression free survival Figure 2: Overall survival Figure 2:. Overall survival Disclosures Waal de: Jansen Cilag: Research Funding. Munck de:Jansen Cilag: Research Funding. Woolthuis:Jansen Cilag: Research Funding. velden Van Der:Jansen Cilag: Research Funding. Tromp:Jansen Cilag: Research Funding. Hoogendoorn:Jansen Cilag: Research Funding. Vellenga:Jansen Cilag: Research Funding. Hovenga:Jansen Cilag: Research Funding.

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An Exploration of Trifluridine/Tipiracil in Combination with Irinotecan in Patients with Pretreated Advanced Gastric Cancer

10.21203/rs.3.rs-1143619/v1 ◽

2021 ◽

Author(s):

Takuro Mizukami ◽

Keiko Minashi ◽

Hiroki Hara ◽

Tomohiro Nishina ◽

Yusuke Amanuma ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Treatment Options ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Heavily Pretreated ◽

Pretreated Patients ◽

Grade 3 ◽

Recommended Phase Ii Dose

Abstract Background: Trifluridine/tipiracil (FTD/TPI) and irinotecan are treatment options for heavily pretreated patients with advanced gastric cancer but with limited efficacies. We investigated the combination of FTD/TPI and irinotecan for such patients.Methods: Patients who refractory to fluoropyrimidine, platinum and taxane were enrolled into four cohorts (Level 1A/1B/2A/2B) used an escalated dose of irinotecan [100 (Level 1) or 125 mg/m2 (Level 2) on days 1 and 15] with 2 schedules of FTD/TPI 35 mg/m2/dose: twice daily, on days 1-5 and 8-12 (Level A) or on days 1-5 and days 15-19 (Level B) of a 28-day cycle. The primary and secondary objectives were determination of maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) , and evaluation of disease control rate (DCR), respectively. Results: Eleven patients were enrolled; 2 at Level 1A, 3 at Level 1B and 6 at Level 2B. DLTs occurred in 2/2 patient at Level 1A, and 2/6 patients at Level 2B. Grade 3 or higher treatment-related adverse events were neutropenia (90.9%), leukopenia (54.5%), anemia (45.5%) and febrile neutropenia (18.2%). One patient at Level 2B achieved partial response and the DCR was 72.7% (95% CI 39.0- 94.0%). The median progression-free survival and overall survival was 3.0 months (95% CI 0.92- not reached) and 10.2 months (95% CI 2.2- not reached), respectively.Conclusion: The RP2D of FTD/TPI combined with irinotecan was determined to be Level 1B with manageable hematologic toxicities and feasible non-hematologic toxicities. Further evaluation for its efficacy in the RP2D is necessary. Mini-abstract: A phases Ib study of trifluridine/tipiracil in combination with irinotecan for advanced gastric cancer determined the recommended dose with manageable hematologic toxicities and feasible non-hematologic toxicities.

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