scholarly journals Real-World Survival in Patients with Metastatic Melanoma after Discontinuation of Anti-PD-1 Immunotherapy for Objective Response or Adverse Effects: A Retrospective Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Julie Valentin ◽  
Thomas Ferté ◽  
Valérie Dorizy-Vuong ◽  
Léa Dousset ◽  
Sorilla Prey ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Metastatic Melanoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Discontinuation Of Treatment

Objective. Anti-PD-1 has dramatically improved the survival of patients with advanced melanoma. However, there is a lack of data on maintenance of the response after treatment discontinuation. We aimed to evaluate the progression-free survival (PFS) of patients with metastatic melanoma after anti-PD-1 interruption for objective response (OR) or limiting toxicity during clinical trials. Methods. All patients with advanced melanoma who stopped single-agent anti-PD-1 antibodies for objective response or toxicity were included between April 2014 and January 2019 in our institution (data cut-off, September 10th, 2019). Clinical and biological factors associated with relapse were studied. Results. The median follow-up after introduction of treatment was 36.5 months [4.6–62.4], and the median follow-up after discontinuation of treatment was 15.7 months (2.5–45.1). Out of 65 patients, 28 patients stopped immunotherapy for limiting adverse effects (AEs) (43.1%), 25 for complete response (CR) (38.4%), and 12 for partial response (PR) or long-term stable disease (SD) (18.5%). Twelve patients relapsed (18.5%) after a median time of 9 months [1.9–40.9 months]. Seven relapsed after discontinuation for AEs, 3 after discontinuation for CR, and 2 after discontinuation for PR/SD. The median PFS after therapy discontinuation was not reached. No statistical association was found between recurrence and age, sex, increased LDH, BRAF status, presence of brain metastases, previous treatments, radiotherapy, or time on anti-PD-1 treatment. Conclusion. This cohort shows a global recurrence rate of 18.5% and confirms a long-lasting response after anti-PD-1 cessation regardless of the cause of discontinuation.

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.

Long-term follow-up outcomes and treatment among patients previously treated with Zizao Yangrong granules (ZYG) for egfris–related skin xerosis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24054-e24054
Author(s):  
Chongxiang Xue ◽  
Jia Li ◽  
Xingyu Lu ◽  
Huijuan Cui
Keyword(s):  
Quality Of Life ◽  
Vitamin E ◽  
Adverse Effects ◽  
Survival Data ◽  
Progression Free Survival ◽  
Complete Response ◽  
Dermatologic Toxicity

e24054 Background: Traditional Chinese medicine (TCM) has broad prospects in the treatment of targeted drugs–related dermatologic toxicity. In our previous study (ChiCTRIOR-17013498), Zizao Yangrong granules (ZYG) made effect on EGFRIs-related xerosis and improve the quality of life. However, some people still doubt that TCM could affect therapeutic benefit for patients treated with EGFRIs. Methods: Patients with EGFRIs related xerosis who underwent ZYG and vitamin E ointment from May 2016 to January 2018 were retrospectively reviewed. Survival data and quality of life data analysis were performed. Besides, patients who used ZYG for more than 8 weeks were also summarized, followed by telephone follow-up and questionnaire survey. Results: Of 68 participates randomly assigned, 54 patients were successfully followed up. Median PFS in Vitamin E Ointment plus ZYG group was 41.6 months, and that in Vitamin E Ointment group was 40.9 months, with no statistical difference (HR 0.85, 95% CI 0.48 to 1.51, P = 0.586). Subsequently, 19 patients who used ZYG for longer than 8 weeks were also included. 2 patients reported complete response, 14 patients reported partial response, and 3 patients reported no response. The overall effective rate was 84.2%. The total DLQI score of patients with long-term intervention of ZYG was 4.47±3.10. Compared with baseline DLQI score (7.00±2.91), the DLQI of patients after ZYG intervention has been significantly improved (P = 0.000). During the continuous use of ZYG treatment, incidence of adverse effects was 57.9%. Treatment-related adverse reactions were mostly mild, with no grade 3/4 adverse events. Conclusions: ZYG did not affect progression free survival of patients treated with EGFRIs. And long time-scale ZYG intervention could continuously relieve EGFRI-related xerosis and significantly improve the quality of life of patients without serious adverse effects. Clinical trial information: ChiCTRIOR-17013498.

CheckMate 067: Long-term outcomes in patients with mucosal melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10019-10019 ◽  
Author(s):  
Alexander Noor Shoushtari ◽  
John Wagstaff ◽  
Paolo Antonio Ascierto ◽  
Marcus O. Butler ◽  
Christopher D. Lao ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Mucosal Melanoma ◽  
Safety Outcomes ◽  
Grade 3 ◽  
Intent To Treat ◽  
Event Rates

10019 Background: Mucosal melanoma is a rare but aggressive malignancy with a poor prognosis. Here we report 5-y outcomes in a subgroup of patients with mucosal melanoma treated in CheckMate 067 with nivolumab plus ipilimumab (NIVO+IPI), NIVO alone, or IPI alone. Methods: Patients with previously untreated stage III or IV melanoma were randomized 1:1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo until progression or unacceptable toxicity. Mucosal histology was not a stratification factor, and patients with mucosal melanoma were identified by local investigators in the study. Descriptive subgroup analyses were performed to evaluate efficacy (objective response rate [ORR], progression-free survival [PFS], overall survival [OS]), and safety. Results: A total of 79 patients with mucosal melanoma were treated. With a minimum follow-up of 60 mo, NIVO+IPI treatment was associated with the highest 5-y ORR (43% [vs 30% with NIVO and 7% with IPI]), PFS (29% [vs 14% and 0%, respectively]), and OS (36% [vs 17% and 7%, respectively]; Table), consistent with trends in the intent-to-treat (ITT) population; however, efficacy outcomes were generally less favorable overall relative to the ITT population. Complete response rates were higher with NIVO+IPI (14%) relative to monotherapy (NIVO, 4%; IPI, 0%) in patients with mucosal melanoma. Safety outcomes, including the grade 3/4 treatment-related adverse event rates of 54%, 26%, and 25%, respectively, were similar to the ITT population. Conclusions: This 5-y analysis showed that patients with mucosal melanoma in CheckMate 067 had similar safety outcomes but poorer long-term efficacy vs the ITT population. Patients with mucosal melanoma treated with NIVO+IPI appeared to have more favorable survival outcomes than those treated with NIVO or IPI alone. Novel therapies are needed to further improve long-term benefit in patients with mucosal melanoma. Clinical trial information: NCT01844505. [Table: see text]

Nivolumab (NIVO) + low-dose ipilimumab (IPI) in previously treated patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 635-635 ◽  
Author(s):  
Michael J. Overman ◽  
Sara Lonardi ◽  
Ka Yeung Mark Wong ◽  
Heinz-Josef Lenz ◽  
Fabio Gelsomino ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Long Term Follow Up ◽  
Previously Treated ◽  
Grade 3

635 Background: In the phase II CheckMate-142 trial, NIVO + low-dose IPI (1 mg/kg) provided meaningful clinical benefit in previously treated MSI-H/dMMR mCRC pts after a median follow-up of 13.4 mo. Here, we present long-term follow-up (median 25.4 mo) of these pts. Methods: Pts received NIVO 3 mg/kg + low-dose IPI Q3W (4 doses) followed by NIVO 3 mg/kg Q2W until disease progression. Primary endpoint was investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. ORR and disease control rates (DCR) were 58 and 81%, respectively (Table). Complete response (CR) rate increased with long-term follow-up from 3 (13.4 mo) to 6% (25.4 mo). Median duration of response (DOR) was not reached, with 68% of responses ongoing at data cutoff. At 24 mo, progression-free survival (PFS) and overall survival (OS) rates were 60 and 74%, respectively; OS rates were 96, 56, and 29% in pts with CR or partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 31% of pts; 10% (grade 3–4) and 13% (any grade) of pts had TRAEs leading to discontinuation. Conclusions: Long-term follow-up with NIVO + low-dose IPI provides durable clinical benefit with deepening of response and a manageable safety profile with no new safety signals, demonstrating long-term benefit of NIVO + low-dose IPI for previously treated pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

scholarly journals Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

2021 ◽  
Author(s):  
Jedd D. Wolchok ◽  
Vanna Chiarion-Sileni ◽  
Rene Gonzalez ◽  
Jean-Jacques Grob ◽  
Piotr Rutkowski ◽  
...  
Keyword(s):  
Descriptive Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
End Points ◽  
Unresectable Stage

PURPOSE In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes. PATIENTS AND METHODS Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated. RESULTS Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF–wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed. CONCLUSION These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.

Association between complete response and survival in advanced melanoma treated with talimogene laherparepvec (T-VEC) plus ipilimumab (ipi).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10029-10029 ◽  
Author(s):  
Jason Alan Chesney ◽  
Igor Puzanov ◽  
Frances A. Collichio ◽  
Mohammed M. Milhem ◽  
Axel Hauschild ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Burden ◽  
Advanced Melanoma ◽  
Stage Iiib ◽  
Ecog Performance Status ◽  
Kaplan Meier

10029 Background: This is the first randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor for advanced melanoma. At the 3-year (yr) follow-up, the combination (combo) of T-VEC and ipi demonstrated durable and statistically superior objective response rate (ORR) over ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% Cl, 1.6–6.0; P = 0.002). Complete response (CR) rate was 21.4% with the combo and 6.0% with ipi. Median overall survival (OS) was not reached in either arm. In this post hoc analysis, we utilized the 3-yr landmark data to explore the relationship between CR and OS in the combo arm. Methods: Pts with unresectable, stage IIIB-IV melanoma were randomized 1:1 to receive combo or ipi alone. T-VEC was administered intratumorally on day 1 of week (wk) 1 at 106 plaque-forming units (PFU)/mL followed by subsequent doses at 108 PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were OS, progression-free survival, and safety. Results: 198 pts were randomized (98 to combo; 100 to ipi). As of February 25, 2019, the median follow-up time was 40.0 mos (range: 0.2–63.7) for the combo arm. Among 98 pts who received combo, 21 (21.4%) had a best overall response of CR including 8 who converted from an initial partial response (PR), 15 (15.3%) had PR, 19 (19.4%) had stable disease, 30 (30.6%) had progressive disease, and 13 (13.2%) were unevaluable. Of 21 pts achieving CR, 17 (81%) had ECOG status of 0, 16 (76.2%) had stage IIIB-IVM1a disease, and 16 (76.2%) had no visceral metastases. Median duration of CR was not reached (range: 5.4[+]–58.2[+] mos); 19 of 21 CRs lasted more than 6 months. The baseline tumor burden was lower in pts with CR than in those with non-CR. Median OS was not reached in pts with CR (range: 25.1[+]–63.7[+] mos) and was 47.6 mos (range: 0.2[+]– 63.7[+] mos) in pts with non-CR (Log-rank P = 0.0005). The Kaplan–Meier estimated 3-year OS rate was 100.0% for patients with CR and 52.3% for those with non-CR. Conclusions: CR rate was higher with T-VEC plus ipi than with ipi alone in pts with advanced melanoma (21.4% vs. 6.0%). In the combo arm, CR was associated with prolonged OS, and pts with CR tended to have better ECOG performance status, earlier-stage disease, and lower baseline tumor burden, as compared with those with non-CR. Clinical trial information: NCT01740297.

Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7513-7513
Author(s):  
Johannes Düll ◽  
Kami J. Maddocks ◽  
Eva Gonzalez-Barca ◽  
Wojciech Jurczak ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Efficacy Analysis

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]

Single-arm phase II study of low-dose paclitaxel and pembrolizumab in platinum-refractory metastatic urothelial carcinoma (UC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 433-433
Author(s):  
Rhonda L. Bitting ◽  
Donald Charles Vile ◽  
Janet A. Tooze ◽  
Christopher Y. Thomas ◽  
Morgan Neve ◽  
...  
Keyword(s):  
Phase Ii ◽  
Low Dose ◽  
Immune Cell ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Intention To Treat ◽  
Definitive Therapy ◽  
Platinum Refractory

433 Background: Single agent checkpoint inhibition is effective in a small proportion of platinum-refractory UC patients but improvements are needed. UC is highly inflammatory, and low-dose chemotherapy may enhance the response to immunotherapy. We evaluated whether combination therapy with low-dose paclitaxel and pembrolizumab is more efficacious than single-agent pembrolizumab which had an objective response rate (ORR) of 21% in a similar patient population in the KEYNOTE-045 study. We also incorporated multiple novel biomarker studies to explore immune regulatory mechanisms in UC. Methods: This is a prospective, single-arm phase II trial (NCT02581982) of pembrolizumab combined with low-dose paclitaxel in patients with platinum-refractory metastatic UC. Key inclusion criteria included measurable progression of disease within 12 months of platinum therapy and ECOG ≤1. Patients received pembrolizumab 200mg day 1 and paclitaxel 80 mg/m2 days 1 and 8 of a 21 day cycle for up to 8 cycles unless clinical or radiographic disease progression or unacceptable adverse events (AEs) were observed. Responding patients could remain on pembrolizumab maintenance for up to 2 years. The primary endpoint was ORR; key secondary endpoints included overall survival (OS), 6-month progression free survival (PFS), and safety. Results: Twenty-seven patients were treated between 4/2016 - 6/2020, with a median follow up of 9.9 months. At baseline, the median age was 68 years (range 49-80), with 81% men and 78% non-Hispanic white. The majority (59%) were ECOG 1. Twenty-one of 27 (78%) received prior definitive therapy: chemoradiation in 24% and surgery in 76%. The majority (78%) of patients received prior cisplatin. 70% progressed on a cisplatin-based regimen while 30% progressed on carboplatin-based regimen within 12 months of study entry. The ORR by intention to treat was 9 of 27 patients (33%) and in patients evaluable for response by imaging was 9 of 25 (36%), including 3 with complete response. Disease control rate in evaluable patients was 72%. Six-month PFS was 46.8% (95% CI: 27.2%, 64.2%) and median OS was 11.7 months (95% CI: 8.7 mo, NR). Common ≥ grade 2 AEs were anemia (44%), lymphopenia (37%), hyperglycemia (33%), and fatigue (33%). Possible treatment-related at least grade 3 or 4 AEs occurred in 56% of subjects, including 2 immune-mediated AEs (pneumonitis and nephritis) resulting in therapy cessation but a durable partial response. There were no grade 5 events. Conclusions: This study illustrates that the addition of low-dose paclitaxel to pembrolizumab improves outcomes in patients with platinum-refractory UC, relative to single-agent pembrolizumab. No unanticipated safety signals emerged. Exploratory analyses including PDL1 status, tumor mutational burden, and change in circulating microRNAs and in immune cell populations are ongoing. Clinical trial information: NCT02581982.

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

scholarly journals Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Caitlyn N. Myrdal ◽  
Srinath Sundararajan
Keyword(s):  
Targeted Therapy ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Mek Inhibitor ◽  
Optimal Sequencing ◽  
The Right

Little is known about the optimal sequencing of targeted therapy and immunotherapy in the treatment of patients with BRAFV600-mutated metastatic melanoma. BRAF/MEK inhibition often has the benefit of rapid disease regression; however, resistance is frequently seen with long-term use. Treatment with immune checkpoint inhibitors offers the potential for long-term response but displays a lower rate of objective response. The benefit of synergy between therapies is apparent; however, there is limited data regarding optimal sequencing in the treatment of advanced melanoma. We present the case of a 62-year-old gentleman with advanced BRAFV600-mutated melanoma who followed an unconventional treatment path. After progressing on single-agent vemurafenib, he had response to multiple modalities of immunotherapy before progression. After, he had a substantial response to multiple BRAF/MEK inhibitor rechallenges before developing resistance. The patient is now stable after a retrial of combination immunotherapy. Our case illustrates that with the right sequencing of therapy, meaningful clinical responses can be elicited with rechallenging of targeted therapy and immunotherapy in metastatic melanoma.

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