A randomized phase II study of chemoradiation (CRT) +/- nivolumab (Nivo) with sequential safety evaluations of Nivo +/- lirilumab (Liri) or ipilumumab (Ipi) concomitant with (C) RT in intermediate (IR) and high-risk (HR) head and neck squamous cell carcinoma (HNSCC) (RTOG 3504, NCT02764593).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS6097-TPS6097 ◽  
Author(s):  
Maura L. Gillison ◽  
Robert L. Ferris ◽  
Qiang Zhang ◽  
A. Dimitrios Colevas ◽  
Loren K. Mell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Safety Evaluation ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Programmed Death ◽  
Secondary Endpoints ◽  
Platinum Refractory ◽  
Programmed Death 1

TPS6097 Background: Nivolumab (Nivo), a monoclonal antibody to the programmed death-1 (PD-1) immune checkpoint receptor, improved overall survival (OS) for patients (pts) with platinum-refractory, recurrent/metastatic HNSCC compared with standard therapy. A placebo controlled phase IIR trial was designed to investigate the hypothesis that Nivo added to platinum-based CRT will improve progression free survival (PFS) for pts with newly diagnosed IR/HR HNSCC. Methods: Eligibility includes IR HNSCC (p16+, oropharynx T1-2N2b-N3/T3-4N0-3, > 10 pack-years (pys) or T4N0-N3, T1-3N3 ≤ 10 pys) and HR HNSCC (oral cavity, larynx, hypopharynx, or p16(-) oropharynx, stage T1-2N2a-N3 or T3-4N0-3). After safety evaluation in 8 evaluable pts, 176 pts will be randomized (1:1) to cisplatin (40 mg/m2/week X 7) with radiation (IMRT, 70 Gy in 7 weeks) +/- Nivo/placebo (240 mgs q14 days X 5, then 480 mgs q28 X3). Primary endpoint is PFS. Secondary endpoints include OS, acute and chronic toxicity, quality of life and biomarkers (tumor PD-L1 expression; E6/7 seroreactivity and frequency of functional circulating and intraumoral T cells). Parallel with Phase IIR are sequential safety evaluations (see Table) in platinum eligible and ineligible ( > 70 years; ≥3 grade neuropathy; ≥2 hearing loss; or CrCl < 60 ml/min) cohorts (N = 10-20) of Nivo +/- Liri (anti-KIR) or Ipi (anti-CTLA4) concomitant with RT alone, cisplatin-RT or cetuximab-RT platforms followed by 3 months of adjuvant immunotherapy. The primary endpoint is safety and feasibility. With 8 evaluable pts, the probability of treatment assessed as toxic is > 78% when the true toxicity rate is > 45% and treatment assessed tolerable is > 80% if the true toxicity rate is < 20%. Clinical trial information: NCT02764593. [Table: see text]

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

PARTNER: A randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6029-6029 ◽  
Author(s):  
Lori J. Wirth ◽  
Shaker R. Dakhil ◽  
Gabriela Kornek ◽  
Rita Axelrod ◽  
Douglas Adkins ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Hpv Status ◽  
Secondary Endpoints ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Clinical Trial Information

6029 Background: PARTNER was a multicenter, randomized phase II estimation study evaluating 1stEline tx of R/M SCCHN with doc/cis ± pmab. Methods: Patients (pts) were randomized 1:1 to doc/cis with pmab (Arm 1) or doc/cis alone (Arm 2). Arm 1 received 9 mg/kg pmab on day 1 of each 21-day cycle, and all pts received 1stEline doc/cis both at 75 mg/m2 on day 1 for up to 6 cycles. In Arm 1, pts could receive pmab monotherapy upon completion of 6 cycles of doc/cis until disease progression (PD). In Arm 2, pts could receive pmab as 2ndEline monotherapy upon PD. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. HPV status was determined using p16 INK IHC. No formal hypothesis was tested. Results: Baseline characteristics were balanced between arms. Of 103 pts, HPV status was evaluable in 66 (64%); 29% were HPV positive. Efficacy results are shown (Table). Worst grade 3/4 adverse events (AEs) were 73% in Arm 1 vs 56% in Arm 2. Conclusions: Median PFS was increased in both arms over historical doublet cytotoxic chemotherapy. PFS and ORR were higher in the pmab arm in the overall population, in the HPV positive (n=19) group, and in the HPV negative (n=47) group. There was an increase in grade 3/4 AEs with this regimen. The crossover design, with 57% of Arm 2 pts receiving pmab as 2ndEline monotherapy, confounds interpretation of OS. Clinical trial information: NCT00454779. [Table: see text]

Phase II trial of oral etoposide plus IV irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5537-5537
Author(s):  
Koji Matsumoto ◽  
Noriyuki Katsumata ◽  
Taro Shibata ◽  
Tadao Takano ◽  
Ryuichiro Nishimura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Threshold Value ◽  
Oral Etoposide ◽  
Stage Design ◽  
Free Survival ◽  
Medical Needs ◽  
Secondary Endpoints

5537 Background: Developing effective chemotherapy for patients (pts) with platinum (Pt) resistant ovarian cancer is unmet medical needs. Topoisomerase inhibitors, such as oral etoposide and iv irinotecan, have been reported to show some efficacy for Pt - resistant ovarian cancer as monotherapy. Combining these two agents should be an intriguing idea. Following phase 1 and feasibility study reported in ASCO2002 and 2005, this study aimed to assess safety and efficacy of oral etoposide plus iv irinotecan for pts with Pt -resistant and taxane pre-treated ovarian cancer (UMIN-CTR ID: UMIN000001837). Methods: Eligible pts are given etoposide at 50 mg/m2 p.o. from day 1 to 21, and irinotecan 70 mg/m2iv, at day1 and day15, repeated every 28 days, up to 6 cycles. Primary endpoint is response rate (RR), secondary endpoints are adverse events, progression-free survival (PFS), and overall survival (OS). As a SWOG two-stage design, at least 55 pts are required with one-sided alpha of 0.05, beta of 0.2 and expected and threshold value for primary endpoint as 35% and 20%. Sixty pts are to be registered. Results: From April 2009 to January 2012, 61 pts were entered to this study. One patient was ineligible, thus 60 pts were analyzed for the study. RR was 21.7% (1 CR + 12 PR, 89% C.I. 13.5 – 31.9 %, one-sided p=0.42). At the data cut-off at November 2012, median PFS and OS were 4.1 (95% C.I. 3.5 – 5.6) and 12.4 (95% C.I. 10.1 – 14.8) months, respectively. Six months-PFS was 35.0 %. For pts with Pt --free interval (PFI) >= three months (n = 33), RR was 30.3 % (95% C.I. 15.6 -48.7 %), median PFS and OS was 5.8and 16.9 months, respectively. For safety, G3/4 neutropenia, anemia, and thrombocytopenia were 60.0 %, 36.7 % and 11.7%, respectively. G3/4 non-hematological toxicities over 10 % were febrile neutropenia (FN) (18.3%), fatigue (13.3%), nausea (11.7 %) and anorexia (11.7 %). FN was more frequent in elderly pts of 65 years or older (28.6 %). Two treatment-related deaths occurred, both in elderly. Conclusions: As a whole, this regimen did not meet primary endpoint for further phase 3 study. Elderly pts should be treated very cautiously with this regimen. However, promising efficacy could be expected for those with PFI >= 3 months. Clinical trial information: UMIN000001837.

Phase III study of lapatinib (L) plus trastuzumab (T) and aromatase inhibitor (AI) vs T+AI vs L+AI in postmenopausal women (PMW) with HER2+, HR+ metastatic breast cancer (MBC): ALTERNATIVE.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1004-1004 ◽  
Author(s):  
William John Gradishar ◽  
Roberto Hegg ◽  
Seock-Ah Im ◽  
In Hae Park ◽  
Sergei Tjulandin ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Clinical Trial Information

1004 Background: Combination ofHER2-targeted therapy+AI improved clinical benefit in patients (pts) with HER2+, HR+ MBC vs AI alone in two previous trials, median progression free survival (mPFS) 4.8 vs 2.4 mo (TAnDEM), and 8.2 vs 3.0 mo (EGF30008). Dual HER2 blockade enhances clinical benefit vs single HER2 blockade. This study evaluated the safety and efficacy of dual vs single HER2 blockade (L+T vs T/L)+AI in HER2+, HR+ MBC progressing on (neo)adjuvant/first-line T+chemotherapy (CT). HER2 and HR status were assessed for eligibility at local lab. Methods: PMW were randomized 1:1:1 to receive T (8mg/kg followed by 6mg/kg IV Q3W)+L (1000mg/d)+AI or T+AI or L (1500mg/d)+AI. AI was per investigator’s choice. Pts were excluded if they were intended for CT. The primary endpoint was to assess superiority of PFS with L+T vs T. Secondary endpoints included PFS (L vs T), overall survival (OS), overall response rate (ORR), and safety. Results: 369 pts were enrolled; current analysis included 355 pts (data cutoff, March 11, 2016); L+T (n = 120), T (n = 117) or L (n = 118). Final PFS data were analyzed after 137 events. Baseline characteristics were balanced across all treatment (tx) arms. The primary endpoint was met; superior PFS was observed with L+T vs T (mPFS, 11 vs 5.7 mo; HR = 0.62, 95% CI [0.45, 0.88], P= 0.0064). This benefit of L+T was consistent in key subgroups. mPFS with L vs T was 8.3 vs 5.7 mo (HR = 0.71, 95% CI [0.51, 0.98], P= 0.0361). ORR with L+T, T, and L was 32%, 14%, and 19% respectively. OS data are immature. Most common adverse events (AEs) with L+T, T and L (≥15%, any arm) were diarrhea (69%, 9%, 51%), rash (36%, 2%, 28%), nausea (22%, 9%, 22%), and paronychia (30%, 0, 15%). Hepatic abnormalities of > 3 ULN ALT/AST levels were noted in 4%, 6%, and 16% respectively. Incidence of tx-related SAEs was 5%, 2%, and 4% and on-tx deaths was 3%, 4%, and 5%, respectively. Conclusions: Dual HER2 blockade with L+T+AI showed superior PFS benefit vs T+AI, in pts with HER2+, HR+ MBC. Incidence of AEs was increased with L+T. This combination can potentially offer an effective CT-sparing tx option in subgroup of HER2+, HR+ pts without aggressive disease and who are not candidates for CT. Clinical trial information: 2010-019577-16.

scholarly journals Efficacy and Safety of Different Doses of Bevacizumab Combined With Pemetrexed and Platinum in First-Line Treatment of Advanced NSCLC: A Retrospective-Real World Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Hua Zhou ◽  
Feng Yang ◽  
Wen-Juan Jiang ◽  
Yong-Chang Zhang ◽  
Hai-Yan Yang ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
The Cost ◽  
Different Doses

Background: Bevacizumab was demonstrated to have efficacy in patients with NSCLC. However, application of different doses of bevacizumab in different clinical trials was overlooked. This study aims to investigate the effects and safety of different doses of bevacizumab in the treatment.Methods: From January 2016 to March 2020, 79 patients with NSCLC received first-line combination treatment with chemotherapy (pemetrexed + platinum) and bevacizumab for four cycles; patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab combined with pemetrexed, of which 57 patients received bevacizumab at a dose of 7.5 mg/kg and 22 patients at a dose of 15 mg/kg. The primary endpoint was progression-free survival, and secondary endpoints were overall response rate, disease control rate, and adverse events.Results: There was no significant difference between two groups in effectiveness; Median PFS in 7.5 mg/kg group and in 15 mg/kg group were 8.0 and 8.7 months, respectively (p = 0.663), reaching the primary endpoint. The ORR and DCR in the bevacizumab 7.5 and 15 mg/kg group were 45.46 and 86.0% vs. 50 and 90.9% showing no statistical significance (p = 0.804 and 0.717). Most of side effects were tolerable. The incidences of overall toxicities were higher in 15 mg/kg group (p = 0.001). No new safety signals were observed.Conclusion: We did not detect significant difference of efficacy and safety between 7.5 mg/kg group and 15 mg/kg group for bevacizumab administration, the cost-effectiveness of the 7.5 mg/kg group was significantly better than that of the 15 mg/kg group.

Efficacy and safety of CetuGEX in recurrent/metastatic squamous cell carcinoma of the head and neck (RM-HNSCC): Results from the randomized phase II RESGEX study.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 59-59 ◽  
Author(s):  
Ulrich Keilholz ◽  
Andrzej Kawecki ◽  
Andreas Dietz ◽  
Bogdan Zurawski ◽  
Michael Schenker ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Primary Endpoint ◽  
Single Agent ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Primary Tumor Site ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Epidermal Growth

59 Background: Standard treatment for RM-HNSCC is a combination of cisplatin (P), 5-FU (F), and the epidermal growth factor receptor (EGFR) blocking monoclonal antibody cetuximab. CetuGEX is a new monoclonal antibody sharing the identical EGFR-binding domain with cetuximab, but a modified Fc part by a proprietary glycosylation method to optimize antibody dependent cellular cytotoxicity (ADCC). Methods: Patients with RM-HNSCC without relevant comorbidities were randomized to receive up to 6 cycles of P 100 mg/m2, F 4 x 1000 mg/m2/24hrs and CetuGEX vs. cetuximab. Initial dose of cetuximab was 400mg/m2, followed by weekly 250 mg/m2. CetuGEX was given as 990 mg, followed by weekly 720 mg. After end of combination treatment, patients received single agent antibody maintenance until disease progression or intolerable toxicity. Stratification factors included FcγRIIIa status, primary tumor site, EGFR pretreatment vs. naïve, and recurrent vs. metastatic disease. Primary endpoint was progression-free survival (PFS) by immune related response criteria (irRC). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR) and overall survival (OS) as well as safety and QoL. Results: During Jan 2014 and Feb 2016, 240 patients were accrued in 34 European centers, of which 123 received cetuximab and 117 CetuGEX. The median follow-up was 15 month until May 2017. No difference was observed for the primary endpoint of PFS by irRC [median 27.7 (CetuGEX) and 26.4 (cetuximab) weeks; HR 1.003; 95%-CI 0.738 – 1.363; p = 0.98]. No advantage of CetuGEX over cetuximab was observed for all other secondary efficacy endpoints and subgroup analyses by stratification factors. Infusion related reactions (IRR) were higher for CetuGEX (38.8%) than for cetuximab (5.7%) (Pearson chi2= 37.08; p < 0.0001), but without sequelae. Conclusions: The RESGEX study is the first head-to-head comparison of an ADCC-optimized to a conventional EGFR-directed antibody. The study failed to show superior efficacy of CetuGEX over cetuximab. Both compounds appear to have the same efficacy and a similar safety profile. Glycosylation changes in the Fc part induced more IRRs. Clinical trial information: NCT02052960.

scholarly journals Comparative Impact of PD-1 and PD-L1 Inhibitors on Advanced Esophageal or Gastric/Gastroesophageal Junction Cancer Treatment: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (16) ◽  
pp. 3612
Author(s):  
SuA Oh ◽  
Eunyoung Kim ◽  
Heeyoung Lee
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Progression Free Survival ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
L1 Use

Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have demonstrated varying effectiveness in treating esophageal or gastric/gastroesophageal junction (G/GEJ) cancer. Hence, this systematic review and meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 treatment in patients with esophageal or G/GEJ cancer by analyzing the types of medications. Randomized controlled trials comparing anti-PD-1/PD-L1 to control therapy were identified by searching PubMed, EMBASE, and ClinicalTrials.gov. The outcomes included overall survival (OS), progression-free survival (PFS) rates, and serious adverse events (SAEs), evaluating the differences in therapy types, including a comparison between PD-1 and PD-L1 inhibitors. Eight studies were included in the analysis. PD-1/PD-L1 inhibitors affected the overall OS rate increment without influencing the PFS rate (HR, 0.837; 95% CI, 0.753–0.929; p = 0.001; HR 0.991; 95% CI, 0.778–1.263; p = 0.942, respectively). Anti-PD-1 was significantly more beneficial for increasing OS and PFS than PD-L1 inhibitors. Anti-PD-1 and PD-L1 use was not significantly associated with SAE development in esophageal or G/GEJ cancer patients. PD-1/PD-L1 inhibitor use was associated with improved OS and PFS rate increase among PD-1 and PD-L1 inhibitors. Considering response variations to anti-PD-1/PD-L1 usage, more individualized treatments should be introduced in clinical practice.

Nivolumab (Nivo) vs investigator’s choice (IC) in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Efficacy and safety in CheckMate 141 by prior cetuximab use.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6020-6020 ◽  
Author(s):  
Robert L. Ferris ◽  
Lisa Licitra ◽  
Jérôme Fayette ◽  
Caroline Even ◽  
George R. Blumenschein ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Platinum Refractory ◽  
Grade 3 ◽  
Favorable Safety ◽  
Event Rates

6020 Background: In CheckMate 141, nivo resulted in significantly prolonged overall survival (OS), favorable safety, and stable quality of life vs IC in patients (pts) with platinum-refractory (PR) R/M SCCHN. Cetuximab, a formal trial stratification factor, permits exploratory subgroup assessment. Outcomes by prior cetuximab use are described. Methods: CheckMate 141 was a randomized, open-label, phase 3 trial (NCT02105636) in which pts (N = 361) with PR R/M SCCHN were randomized 2:1 and stratified by prior cetuximab use to nivo 3 mg/kg every 2 weeks or IC of methotrexate, docetaxel, or cetuximab. The primary endpoint was OS; additional endpoints were progression-free survival (PFS), objective response rate (ORR), and safety. A multivariate analysis will explore influence of additional factors. Results: Nivo improved OS vs IC regardless of prior cetuximab, and improvement was greater in pts without prior cetuximab (Table). Median OS was longer for nivo vs IC in pts with PD-L1 expression ≥ 1% regardless of prior cetuximab, and in pts with PD-L1 expression < 1% without prior cetuximab. Among pts with PD-L1 expression ≥ 1%, ORR was higher with nivo vs IC with/without prior cetuximab. PFS was similar regardless of prior cetuximab. Grade 3–4 treatment-related adverse event rates for nivo vs IC were 11.7% vs 40.9% with prior cetuximab and 15.4% vs 26.7% without prior cetuximab. Conclusions: OS and ORR improved with nivo vs IC regardless of prior cetuximab use, and the magnitude of benefit was greater in pts without prior cetuximab exposure. These results support the use of nivo for R/M SCCHN regardless of prior cetuximab use. Clinical trial information: NCT02105636. [Table: see text]

scholarly journals Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

2017 ◽  
Vol 35 (2) ◽  
pp. 226-235 ◽  
Author(s):  
Sandra P. D’Angelo ◽  
James Larkin ◽  
Jeffrey A. Sosman ◽  
Celeste Lebbé ◽  
Benjamin Brady ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Programmed Death ◽  
Programmed Death 1

Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

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