Pembrolizumab monotherapy for patients with advanced MSI-H colorectal cancer: Longer-term follow-up of the phase II, KEYNOTE-164 study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
Luis A. Diaz ◽  
Dung T. Le ◽  
Tae Won Kim ◽  
Eric Van Cutsem ◽  
Ravit Geva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Antitumor Immunity ◽  
Best Response ◽  
Grade 5 ◽  
Independent Review ◽  
Secondary Endpoints ◽  
Grade 3

4032 Background: Pembrolizumab provides effective antitumor immunity and durable responses in patients (pts) with advanced, colorectal cancer (CRC) with microsatellite instability-high (MSI-H) tumors. We present data on antitumor immunity with pembrolizumab in pts from the phase 2, KEYNOTE-164 study who had approximately 3 years of follow-up, and in pts re-treated after disease progression. Methods: KEYNOTE-164 enrolled pts with metastatic MSI-H CRC, MSI-H status confirmed locally by IHC or PCR, and ≥2 (cohort A) or ≥1 (cohort B) prior lines of therapy (fluoropyrimidine, oxaliplatin, irinotecan, or anti VEGF/EGFR). Eligible pts received pembrolizumab 200 mg Q3W for 2y (35 administrations) or until progression, unacceptable toxicity, or withdrawal. Pts who stopped pembro due to a confirmed CR or after completing 2y of treatment and who progressed after stopping were eligible for re-treatment with up to 17 administrations in the second-course phase, at investigator discretion. Tumor response was assessed Q9W per RECIST v1.1 by independent review. The primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. The data cutoff date was Sep 9, 2019. Results: At data cutoff, the median follow-up was 31.4 mo (range, 0.2-47.8) for 61 pts in cohort A and 36.1 mo (0.1-39.3) for 63 pts in cohort B. ORR was 32.8% (3CR, 17PR; 95% CI% 21.3-46.0) for cohort A and 34.9% (8CR, 14PR; 95% CI 23.3-48.0) in cohort B. Median DOR was not reached (NR [range, 6.2-41.3+]) and not reached (range, 3.9+ to 37.1+), respectively. Fifteen pts in cohort A and 17 in cohort B had ongoing responses at data cutoff. Median PFS was 2.3 mo (95% CI 2.1-8.1) with 3-yr PFS rate of 31% in cohort A and was 4.1 mo (2.1-18.9) with 3-yr PFS rate of 34% in cohort B. Median OS was 31.4 mo (21.4-NR) with 3-yr OS rate of 49% in cohort A and was not reached (19.2-NR) with 3-yr OS rate of 52% in cohort B. Nine pts (6 in cohort A, 3 in cohort B) had a second course of treatment. The best response in second course was PR in 1 patient each in cohort A and B. Grade 3-4 drug-related adverse events occurred in 10 (16%) pts in cohort A and 8 (13%) pts in cohort B. No grade 5 drug-related events occurred. Conclusions: After approximately 3 y of follow-up, pembrolizumab continues to provide effective long-term antitumor immunity with durable responses, with small numbers of drug-related adverse events and no drug-related deaths in pts with advanced, MSI-H CRC. Clinical trial information: NCT02460198 .

Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
Charu Aggarwal ◽  
Mary Weber Redman ◽  
Primo Lara ◽  
Hossein Borghaei ◽  
Philip C. Hoffman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Grade 5 ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9055 Background: LungMAP is a National Clinical Trials Network umbrella trial for previously-treated SqNSCLC. S1400D is a phase II biomarker-driven therapeutic sub-study evaluating the FGFR inhibitor AZD4547 in patients (pts) with FGFR positive chemo-refractory SqNSCLC. Methods: Eligible pts had tumor FGFR alteration and/or mutation by next generation sequencing (Foundation Medicine), measurable disease, Zubrod PS 0-2, progression after 1 line of systemic therapy, and adequate end organ function. Receipt of prior immunotherapy was allowed. Eligible pts received AZD4547 80 mg bid orally. Primary endpoint was overall response rate (ORR) by RECIST; secondary endpoints included progression-free survival (PFS) and duration of response (DoR). Originally designed as a randomized trial of AZD4547 versus docetaxel, it was redesigned to be a single arm AZD4547 trial with the emergence of immunotherapy as standard 2ndline therapy. Forty pts were required to rule out an ORR of < = 15% if the true ORR was > 35% (90% power, alpha 0.05). Results: 93 pts (13% of pts screened on S1400) were assigned to S1400D; 43 were enrolled with 28 receiving AZD4547. Pt characteristics: median age 66.3 y (49-88), female (n = 8, 29%), & Caucasian (n = 25; 89%). Biomarker profile: FGFR1 amplification (n = 38; 86%); FGFR3 S249C (n = 4; 9%); FGFR3 amplification (n = 3; 7%); and FGFR3 fusion (n = 2; 5%). Nine pts (26%) had more than one biomarker alteration. The study was closed at interim analysis for futility in October 2016. Treatment related Grade 3 AEs were seen in 5 pts (dyspnea, fatigue, hyponatremia, lung infection & retinopathy); 1 pt had Grade 4 sepsis. There were no Grade 5 AEs. Median follow up among alive pts was 4.3 months (mos). Of 25 response evaluable pts, one with FGFR3 S249C had unconfirmed PR (4%, 95% CI 1-20%) with DoR of 1.5 mos. Median PFS was 2.7 mos (95% CI 1.4 - 4.3 mos). Conclusions: This is the first Phase II trial to evaluate AZD4547 as a targeted approach in pts with previously treated FGFR-altered SqNSCLC. AZD4547 had an acceptable safety profile but minimal activity in this biomarker-enriched cohort. Evaluation of other targeted agents in LUNG-MAP is currently ongoing. Clinical trial information: NCT02965378.

Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC) and brain metastases in the pivotal randomized phase 2 ALTA trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20502-e20502 ◽  
Author(s):  
Sai-Hong Ignatius Ou ◽  
Marcello Tiseo ◽  
D. Ross Camidge ◽  
Myung-Ju Ahn ◽  
Rudolf M. Huber ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Review Committee ◽  
Small Cell Lung ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
A Site ◽  
To Receive ◽  
Clinical Trial Information

e20502 Background: The CNS is often a site of first disease progression in CRZ-treated ALK+ NSCLC. The ALTA trial is assessing BRG, an investigational next-generation ALK inhibitor, in pts with CRZ-refractory advanced ALK+ NSCLC, including pts with baseline brain metastases. Methods: In ALTA (NCT02094573), pts were stratified by presence of baseline brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Here, we show data for pts with baseline brain metastases. An independent review committee (IRC) assessed intracranial efficacy. Results: Of 222 pts (112 in arm A; 110 in arm B), 80 (71%)/74 (67%) in A/B had baseline brain metastases per investigators, with median age 49/55 y; 74%/76% had received chemotherapy. As of May 31, 2016, 51%/59% of these pts continued to receive BRG in A/B; median follow-up was 9.6/11.4 mo. Intracranial efficacy is shown in the table. Among these pts, most common treatment-emergent adverse events were: nausea 35%/46% (A/B), headache 30%/31%, vomiting 29%/31%, diarrhea 21%/38%, cough 25%/32%; grade ≥3: increased blood CPK 1%/12%, hypertension 4%/7%, increased lipase 4%/3%. Conclusions: BRG yielded substantial intracranial responses with robust iPFS and acceptable safety in ALK+ NSCLC pts with baseline brain metastases in ALTA. 180 mg (with lead-in) showed consistently improved intracranial efficacy compared with 90 mg. Clinical trial information: NCT02094573. [Table: see text]

scholarly journals Long-Term Safety and Efficacy of Dolutegravir in Treatment-Experienced Adolescents With Human Immunodeficiency Virus Infection: Results of the IMPAACT P1093 Study

2019 ◽  
Vol 9 (2) ◽  
pp. 159-165 ◽  
Author(s):  
Rolando M Viani ◽  
Theodore Ruel ◽  
Carmelita Alvero ◽  
Terry Fenton ◽  
Edward P Acosta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Virologic Failure ◽  
Resistance Testing ◽  
Background Regimen ◽  
Immunodeficiency Virus ◽  
Grade 3 ◽  
Hiv 1

Abstract Background P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort. Methods The study enrolled human immunodeficiency virus type 1 (HIV-1)–infected treatment-experienced adolescents aged 12 to &lt;18 years, with an HIV-1 RNA level ≥1000 copies/mL . Cumulative safety and HIV-1 RNA outcomes were assessed once the last enrolled participant reached 144 weeks of follow-up. Results Among 23 adolescents enrolled, 16 remained in the study at least 144 weeks; the median follow-up was 153 weeks (range, 55–193 weeks). Dolutegravir was well tolerated, with grade 3 clinical adverse events in 5 participants, grade 3 laboratory abnormalities in 3, and grade 4 laboratory abnormalities in 1; none of the adverse events or abnormalities were judged to be treatment related. In an-intent-to-treat analysis, an HIV-1 RNA level &lt;400 copies/mL at week 144 was achieved in 43% (10 of 23 participants; 95% confidence interval, 23.2%–65.5%); in addition, 35% (8 of 23; 16.4%–57.3%) had an HIV-1 RNA level &lt;50 copies/mL. Nine participants (39%) discontinued study treatment before 144 weeks, but none because of adverse events or drug intolerance. All participants with sustained virologic control had excellent adherence; most who experienced virologic failure had adherence levels &lt;90%. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change. Conclusions Dolutegravir plus an optimized background regimen seemed safe, well tolerated, and efficacious in this cohort of treatment-experienced HIV-1-infected adolescents. Adherence remains problematic in this population. Clinical Trials Registration NCT01302847.

Long-term Results of Therapy with Sunitinib in Metastatic Alveolar Soft Part Sarcoma

2017 ◽  
Vol 103 (3) ◽  
pp. 231-235 ◽  
Author(s):  
Paulina Jagodzińska-Mucha ◽  
Tomasz Świtaj ◽  
Katarzyna Kozak ◽  
Hanna Koseła-Paterczyk ◽  
Anna Klimczak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Part ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Alveolar Soft Part Sarcoma ◽  
Best Response ◽  
Hand Foot Syndrome ◽  
Grade 3

Background Alveolar soft part sarcoma (ASPS) is a rare, highly vascularized soft tissue sarcoma characterized by a high frequency of metastatic disease and resistance to classical chemotherapy. The purpose of our analysis was to assess long-term sunitinib activity in the treatment of metastatic ASPS. Patients and Methods Between 2009 and 2015, 15 patients were diagnosed with metastatic ASPS and received therapy with sunitinib at initial continuous daily dosing of 37.5 mg. Median age was 32 years. The primary tumor sites were lower extremities ( 8 ), trunk-retroperitoneum/pelvis ( 2 ), upper extremity ( 3 ) and other ( 2 ). All patients had unresectable disease (primary or relapse in the form of metastases to the lungs ± bones). Five patients received systemic therapy before initiating sunitinib. Median follow-up from start of sunitinib was 38 months (range 5-69 months). Results At the time of analysis 4 patients continue therapy and 9 are still alive. Six patients had RECIST partial remission as best response, 8 had stable disease, and 1 had disease progression. The median progression-free survival was 19 months, with 86% of patients being free of progression at 6 months. Median overall survival was 56 months; the 5-year overall survival rate was 49%. Five patients were treated with sunitinib longer than 2 years. All patients experienced some side effects: 8 patients (53%) had CTCAE grade 3/4 toxicity, 7 patients required dose reduction. The most common toxicities were neutropenia, thrombocytopenia, hypothyroidism, arterial hypertension, and hand-foot syndrome. Conclusions Our analysis confirms the long-term efficacy of sunitinib in patients with advanced ASPS.

scholarly journals Long-Term Safety and Efficacy of Orelabrutinib Monotherapy in Chinese Patients with Relapsed or Refractory Mantle Cell Lymphoma: A Multicenter, Open-Label, Phase II Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Yuqin Song ◽  
Yongping Song ◽  
Lihong Liu ◽  
Mingzhi Zhang ◽  
Zhiming Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Chinese Patients ◽  
Severe Bleeding ◽  
Open Label ◽  
Mantle Cell ◽  
Btk Inhibitor ◽  
Grade 3 ◽  
Depth Response

Background: In spite of years of effort, Mantle Cell Lymphoma (MCL) remains a clinical challenge. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitor has been validated with the approvals by FDA for the treatment of multiple subtypes of NHL including refractory and relapse (r/r) MCL. However, some serious adverse events (AEs) due to poor target selectivity (inhibition of EGFR, TEC, BMX and others), such as diarrhea, sever bleeding and atrial fibrillation, remain as challenges in clinic. Orelabrutinib is a novel, potent irreversible BTK inhibitor with high selectivity for BTK. Results of early clinical study showed that it has excellent safety/tolerability profiles and favorable pharmacokinetic/pharmacodynamic properties. Sustained ~100% BTK occupancy at 24 hours was achieved with once daily dosing regimen of 50 mg and above. In this presentation, we will report an updated analysis of orelabrutinib in Chinese patients with r/r MCL with minimum of 12 cycles of treatment. Aims: To evaluate the sustained efficacy and long-term safety of orelabrutinib in Chinese patients with r/r MCL. Methods: This is an open-label, multicenter, two stages, phase II study. The primary endpoint was objective response rate (ORR) assessed per Lugano criteria (2014). Safety and other efficacy (DOR, PFS, OS) evaluations were chosen as secondary endpoints. Results: A Total 106 patients, were enrolled in this study with median follow up time of 15.0 months. 79.2% of the patients were male and median age of 62.0 years old. Most patients were at advanced stage (73.6% were at stage IV and 20.8% were at stage III). According to per protocol analysis, 87 (87.9%) patients achieved ORR and 93.9% patients achieved disease control. The median duration of response (DOR) was not reached, the DOR rate at 12 months was 73.7%, as expected the median PFS and OS were not reached, the PFS and OS rates at 12-month were 70.8% and 88.7% respectively. Comparing to the results of previous analysis, the CR rate, by conventional CT method, increased to 27.4% and it was expected a higher rate of in depth response may occur with prolonged treatment. Further analysis showed orelabrutinib was efficacious in all subgroups (age, gender, status, stage, prior therapy, etc.). Orelabrutinib demonstrated excellent safety profile in r/r MCL patients. The frequently reported treatment related adverse events (TRAE) were primarily hematological toxicities including thrombocytopenia, neutropenia, leukopenia, and hypertension. The frequently reported grade 3 or higher AEs of any cause was thrombocytopenia . No treatment related ≥grade 3 GI and cardio toxicity, nor severe bleeding, were observed. Of the 106 patients, 32 experienced serious AEs; and 17 of them, mainly hematological toxicities and / or infections were treatment-related. Comparing to the safety data of median follow up of 10.5 months, there was only a mild increase of adverse events rate after extended treatments; the safety profiles were essentially the same. These results suggested that safety events primarily occurred during early treatment and it appeared less eventful with orelabrutinib continue treatment. Conclusion: Orelabrutinib showed continuous efficacious in treating patients with r/r MCL. In addition, orelabrutinib is safe and well tolerated with no treatment related grade 3 or higher diarrhea, atrial fibrillation/flutter or severe bleeding in this study. Results of prolong treatment expected to produce a higher rate of in depth response without altering its safety profiles support orelabrutinib being a better selection for BTKi therapy. The improved safety as a resulting of high target selectivity, and the convenience of daily dosing regimen provides orelabrutinib as preferred therapeutic choice for B cell malignancy. Disclosures Zhang: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Xu:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment.

scholarly journals Long-term toxicity and survival outcomes after stereotactic ablative radiotherapy for patients with centrally located thoracic tumors

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Banu Atalar ◽  
Teuta Zoto Mustafayev ◽  
Terence T. Sio ◽  
Bilgehan Sahin ◽  
Gorkem Gungor ◽  
...  
Keyword(s):  
Complete Response ◽  
Lung Tumors ◽  
Tracheobronchial Tree ◽  
Stereotactic Ablative Radiotherapy ◽  
Factors Affecting ◽  
Grade 5 ◽  
Thoracic Cancer ◽  
Grade 3

AbstractBackgroundStereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors.Patients and methodsWe retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses.ResultsAmong 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30–60) Gy in 5 (3–10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48–65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs. lower toxicity (5 vs. 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs. without reirradiation (2-year TFS, 63% vs. 96%; P = 0.02).ConclusionsOur study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.

Brentuximab Vedotin (BV) Plus Rituximab (R) As Frontline Therapy for Patients (Pts) with Epstein Barr Virus (EBV)+ and/or CD30+ Lymphoma: Phase I Results of an Ongoing Phase I-II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3096-3096 ◽  
Author(s):  
Mitul Gandhi ◽  
Shuo Ma ◽  
Sonali M. Smith ◽  
Chadi Nabhan ◽  
Andrew M. Evens ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Dose Reduction ◽  
Research Funding ◽  
Response Data ◽  
Best Response ◽  
History Of ◽  
Frontline Therapy ◽  
Grade 3

Background Although there is no standardized frontline therapy for pts with post transplant lymphoproliferative disorder (PTLD), aggressive induction with chemoimmunotherapy (CIT) is associated in this population with excess toxicity (Choquet, 2007). Recent data support a risk-stratified sequential therapy approach, in which pts receive single-agent R, with aggressive CIT reserved for those not achieving complete response (CR; Trappe, 2012). However, only about 25-30% of pts treated by this method are spared aggressive CIT. Furthermore, elderly pts (eg, EBV-related DLBCL of elderly) and those with autoimmune disorders are prone to lymphoma sharing clinicopathological characteristics with PTLD, such as EBV, CD30, and CD20 coexpression. BV is a novel antibody-drug conjugate that received accelerated FDA approval based on high response rates in pts with relapsed/refractory CD30+ lymphoma. We hypothesized that a combination of BV and R would yield higher response rates than R alone, would limit exposure to CIT, and its attendant toxicity, in these pts. Methods We initiated a Phase I-II trial of the combination of BV and R in adults with previously untreated CD20+ NHL, with co-expression of EBV and/or CD30 (all at any level). Pts with central nervous system involvement, HIV infection, and those lacking history of immunodeficiency, were excluded. Induction consisted of R 375 mg/m2 days 1, 8, 15 22, and BV 1.2 mg/kg, days 1, 8, and 15, followed by restaging. Those with progressive (PD) or stable disease (SD) were removed from protocol and treated per local investigator (CIT recommended). Pts with partial response (PR) or CR could receive a second identical induction, followed by maintenance therapy (MT), or move directly to MT without consolidation. MT consisted of BV 1.8 mg/kg every 3 weeks and R 375 mg/m2 every 6 weeks for up to one year of total therapy. A standard 3 + 3 design was employed for Phase I, with provisional dose reduction in BV to 0.8 mg/kg. Toxicity data was defined using CTCAE 4.0. Response (Cheson, 2007) was assessed, at the end of induction, consolidation (if given), and after cycles 4 and 7 of BV. The primary objective in the phase I portion was to evaluate the safety of the combination of BV and R and to determine the recommended phase II dose (RP2D) of the combination. Results Toxicity and response data are available on seven pts (six treated in Phase I). Four were female, and median age was 61. Five pts had PTLD, diagnosed between 2 and 26 years from transplant, and two had pre-existing autoimmune disease with histories of iatrogenic immunosuppression. Patient characteristics and response data are summarized in Table 1. Five patients (71%) had a CR as best response. At median follow up of 9 months, no pts had PD or had died. One pt with SD as best response achieved CR after CIT, and another with SD declined further therapy but had not progressed at last follow up. Both pts with EBV+ serum by PCR at baseline cleared the virus during therapy. The most frequent Grade 3/4 adverse events (AE) observed were lymphopenia and neutropenia. The most frequent AE of any grade were anemia, transaminitis, and lymphopenia (Table 2). A dose reduction was not required after treatment of the first cohort, but an expansion cohort was requested by the Data/Safety Monitoring Committee for an episode of hyperbilirubinemia (primarly indirect and attributed to blood transfusion). No dose reductions were required during phase I, and the starting dose was the RP2D. Conclusions The combination of BV and R has an acceptable safety profile, appears efficacious and capable of sparing pts exposure to CIT, and warrants further evaluation in patients with CD30+ and/or EBV+ lymphomas with the RP2D idenfitied above. TABLE 1 Characteristics & Outcomes Pt Histology Stage IPI EBV (Serum) CD30 (IHC) Response(Induction) Best Response(Induction or MT) 1 P 4 2 + + CR CR 2* M 1 0 - + PR CR 3 M 3 3 - + PR CR 4 HL 3 1 - + CR CR 5* TCL 1 2 + - SD SD 6 M 4 1 - + SD SD 7 M 3 3 - + CR CR P: Polymorphic; M- Monomorphic large B cell like; TCL- T cell lymphoma; HL- Hodgkin's Like Lymphoma * Immunosuppression Related Lymphoma without history of solid organ transplant TABLE 2 Adverse events occurring in 50% or more of patients (total n=7) Adverse Event Grade 1 & 2 (n) Grade 3 & 4 (n) Anemia 5 1 Abdominal Pain 4 0 Diarrhea 3 0 Nausea 3 0 Fatigue 4 0 Elevated AST 3 2 Hyperbilirubinemia 2 1 Lymphopenia 1 4 Neutropenia 1 3 Anorexia 3 0 Hypoalbuminemia 5 0 Peripheral neuropathy 2 2 Disclosures Nabhan: Celgene: Honoraria, Research Funding. Petrich:Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics : Consultancy, Honoraria, Research Funding, Speakers Bureau.

Nivolumab ± ipilimumab in pts with advanced (adv)/metastatic chemotherapy-refractory (CTx-R) gastric (G), esophageal (E), or gastroesophageal junction (GEJ) cancer: CheckMate 032 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4014-4014 ◽  
Author(s):  
Yelena Yuriy Janjigian ◽  
Patrick Alexander Ott ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Clinical Activity ◽  
Heavily Pretreated ◽  
Long Term Follow Up ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

4014 Background: In the phase 3 ONO-12 study, 3rd- or later-line nivolumab (N) monotherapy prolonged OS vs placebo in Asian pts with adv G/GEJ cancer (median OS, 5.3 vs 4.1 mo; HR, 0.63; P < 0.0001; ASCO-GI 2017, Kang YK et al. J Clin Oncol. 2017;35 (suppl 4S) [abstract 2]). The phase 1/2 CheckMate 032 study showed favorable clinical activity of N ± ipilimumab (I) in Western pts with adv CTx-R G/E/GEJ cancer (NCT01928394). We report updated long-term follow-up data of G/E/GEJ pts in CheckMate 032. Methods: Pts received N 3 mg/kg Q2W (N3), N 1 mg/kg + I 3 mg/kg Q3W (N1+I3), or N 3 mg/kg + I 1 mg/kg Q3W (N3+I1). Primary endpoint was ORR. Secondary endpoints included DOR, OS, PFS, and safety. Efficacy in pts by PD-L1 status was assessed. Results: 160 heavily pretreated pts (79% had ≥ 2 prior Tx) were enrolled (N3, n = 59; N1+I3, n = 49; N3+I1, n = 52); 24% had PD-L1+ (≥ 1%) tumors. ORR was 12% in N3, 24% in N1+I3, and 8% in N3+I1. In pts with PD-L1 ≥ 1%, ORR was 19% (3/16) in N3, 40% (4/10) in N1+I3, and 23% (3/13) in N3+I1; in pts with PD-L1 < 1%, ORR was 12% (3/26), 22% (7/32), and 0% (0/30), respectively. Median DOR was 7.1 mo in N3, 7.9 mo in N1+I3, and NA in N3+I1. OS in all pts and in pts with PD-L1 ≥ 1% is in the Table. Grade 3–4 treatment-related AEs reported in ≥ 10% of pts in any treatment arm were diarrhea (N3, 2%; N1+I3, 14%; N3+I1, 2%), ALT increased (N3, 3%; N1+I3, 14%; N3+I1, 4%), and AST increased (N3, 5%; N1+I3, 10%; N3+I1, 2%). Conclusions: N ± I led to durable responses and long-term OS in heavily pretreated Western pts with adv G/E/GEJ cancer, which is consistent with the clinical activity observed in Asian pts in the ONO-12 study. Safety was consistent with prior reports. These data support ongoing investigation of N ± I in pts with adv G/E/GEJ cancer. Clinical trial information: NCT01928394. [Table: see text]

Long-term immune-related adverse events under PD-1 inhibitors: a multicenter prospective cohort study (MELBASE).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10057-10057
Author(s):  
Charlee Nardin ◽  
Stéphane Dalle ◽  
Marie Thérèse Leccia ◽  
Laurent Mortier ◽  
Sophie Dalac-Rat ◽  
...  
Keyword(s):  
Adverse Events ◽  
Past History ◽  
Real Life ◽  
Stage Iv ◽  
Real Life Setting ◽  
Melanoma Patients ◽  
Grade 3 ◽  
Multicenter Prospective Cohort Study

10057 Background: PD-1 inhibitors (anti-PD1) are frequently associated with immune-related adverse events (IRAE). Since melanoma patients included in clinical trials were frequently treated during two years, data on IRAE occurring after 2 years of treatment are lacking. This study aimed to describe IRAE in melanoma patients treated with anti-PD1 for longer than 2 years in a real-life setting. Methods: Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. All patients who received anti-PD1 for at least 2 years between January 2013 and November 2019 were included. Among them, patients who experienced IRAE and long-term IRAE defined as IRAE occurring after 2 years of anti-PD1 were identified. Results: Among 1849 patients with advanced melanoma included in Melbase, 119 patients received anti-PD1 monotherapy during at least 2 years, from January 2013 to November 2019, with a median follow-up of 41.7 months (25.2-57.5). Patients characteristics at treatment initiation were: male gender (61%), mean age of 63 years old, past history of autoimmune disease (11%), BRAF WT (72%), AJCC stage IV (84%), brain metastases (22%), ECOG 0-1 (88%) and normal LDH (56%). Patients were treated with Nivolumab (n = 53) or Pembrolizumab (n = 66). IRAE occurred in 99 patients (83%) with a median time of 13.3 months (0-53.9), including severe IRAE (grade 3 or 4) in 30 patients (30%). Long-term IRAE, mostly grades 1-2, occurred in 52 patients (43%). Long-term IRAE led to 5 hospitalizations (4%) of which 4 were grades 3-4. Among patients with long-term IRAE, 45 patients (87%) previously experienced IRAE within the first 2 years of anti-PD1 and 29 patients (56%) experienced multiple IRAE. Conclusions: Our data demonstrate that long-term IRAE are frequent especially in patients who already experienced IRAE within the first two years of treatment. These data should be taken into account to establish formal recommendations on the duration of anti-PD1 therapy.

Multi-institutional analysis of synchronous prostate and rectosigmoid cancers.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 33-33
Author(s):  
Corbin Jacobs ◽  
Jacob Trotter ◽  
Manisha Palta ◽  
Yuan Wu ◽  
Christopher Willett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Stage Iv ◽  
Clinical Situation ◽  
Anastomotic Leaks ◽  
Combined Surgery ◽  
Grade 5 ◽  
Duke University ◽  
Grade 3

33 Background: Synchronous prostate cancer (PC) and rectosigmoid (RS) cancer (RSC) is a challenging clinical situation. Methods: A retrospective review of Duke University and Durham VA charts was performed for men with adenocarcinomas of the prostate and RS colon from 1988-2017. Synchronous presentation was defined as symptoms, diagnosis (dx), or treatment (tx) of PC/RSC within 12 months. The primary endpoint was overall survival (OS), calculated from latest dx date. Univariate and multivariate (MVA) Cox regression was performed using STATA 15.1. Results: Among 31,883 men with PC identified, 330 (1%) also had RSC. 54 (16%) were considered synchronous (median age 67, IQR 62-72). PC was more commonly the first dx (59%), and 15 (28%) underwent prostatectomy (n=13) or radiotherapy (RT, n=2) before a dx of synchronous RSC. 26%, 57%, and 17% had stage I, II-III, and IV RSC, respectively. Prostatectomy, LAR, APR, and combined surgery for both PC/RSC was performed in 17 (31%), 24 (44%), 10 (19%), and 2 (4%) men, respectively. 35 (65%) received RT with median RS dose of 50.4 Gy (IQR 50.4-54 Gy) and prostate boost to 66 Gy (IQR 61-72 Gy). 34 (63%) received 5-FU based chemotherapy, 23 (43%) received ADT, and 9 (17%) received no PC-specific tx. After a median follow up of 43 (IQR 21-93) months, there were 34 deaths: 18 (53%) due to RSC, 2 (6%) due to PC, 3 (9%) due to grade 5 toxicity, 7 (21%) due to another malignancy, and 4 (12%) due to unknown cause without recurrence. Grade 5 toxicities resulted from sequential hepatectomy/LAR, combined prostatectomy/APR, and myocardial infarction while on ADT. Crude late grade ≥3 toxicities include 9 (17%) GI and 6 (11%) GU. Two anastomotic leaks <2.3 years after LAR occurred in men who received neoadjuvant prostate RT boost of 70.6-76.4 Gy. Stages II-III (HR 4.3, p=0.02) and IV (HR 16, p<0.01) for RSC but only stage IV (HR 31, p<0.01) for PC were significantly associated with OS on MVA. Among 30 men with stage II-III RSC and non-metastatic PC, 5-FU based chemotherapy (HR 0.34, p=0.04) but no PC-specific tx was significantly associated with OS on MVA. Conclusions: Synchronous RSC is a greater contributor to mortality than PC. Men aged ≥50 with localized PC should undergo colorectal cancer screening prior to tx to evaluate for synchronous RSC.

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