Background

Palbociclib has been approved by the US FDA since 2015 yet safety and efficacy data among Asian patients is limited. This study reports the use of this drug in ER-positive HER2-negative MBC in Hong Kong as real world practice.

Methods

The demographic data, treatment response, and toxicity profile of patients received palbociclib were collected in a prospectively maintained database. Patients were from both the public and private sectors. The study is supported by the Hong Kong Breast Cancer Foundation.

Results

Fifty-four patients who have received palbociclib for the first time were recruited in the database. The median age was 51 year (range 34-81) and all patients were ethnic Chinese. All were post-menopausal by natural state (67%) or by ovarian suppression. Over half (55%) obtained palbociclib from the name-patient program prior to the launch of the drug in Hong Kong in Jan 2017. The proportion of first line use was 30% prior to- and 36% after the official launch of palbociclib. The partner endocrine therapy (ET) was aromatase inhibitor (39% letrozole, 11% exemestane) or fulvestrant (50%). Except for 4 patients, the majority (93%) were started on the standard dose of 125 mg/day. Of those started on 125 mg/day, 43% developed Gd 3 neutropenia, and 7% had Gd 4 neutropenia during the first cycle; 31% had dose reduction to 100 mg/day on second cycle. Other adverse events (AEs) included anemia (4%), thrombocytopenia (9%), stomatitis (5%), hand-foot syndrome (4%), fatigue (4%), and low appetite (4%). All these were Gd 1-2. No patient had neutropenic fever. Response assessment was available in 37 cases. The disease control rate was 70%. Many responded patients had visceral disease (54%) and were heavily pretreated (chemotherapy 1 line 15%, > =2 lines 35%; ET > =2 lines 27%; mTOR inhibitor 12%).

Conclusions

This is the first real world data reporting the preliminary efficacy and AEs of palbociclib among ER-positive HER2-negative MBC patients from Hong Kong. Palbociclib was well tolerated. The experience is consistent with published literature of Palbociclib. The use of palbociclib in Hong Kong is often in the second or later line setting and the cause remains to be elucidated.

Clinical trial identification

Not applicable

Legal entity responsible for the study

N/A

Funding

Pfizer

Disclosure

All authors have declared no conflicts of interest.

Background

Triple negative breast cancer (TNBC) is categorized by a lack in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2). TNBC is known to be more aggressive and lethal than other types of breast cancer because of their highly invasive and migratory ability. However, the mechanisms and main contributors of their metastatic ability are still unclear. ETS transcription factors are related with tumorigenesis in many tissues including breast epithelium. Among them, ELF3 (ESX/ESE1) is an epithelial-specific gene that is specifically associated with breast cancer and has been amplified in early breast cancer. The potential role of ELF3 in cytoplasm is presented, but the mechanism of ability to regulate tumor-associated gene expression and breast cell survival for ELF3 are not yet known. Several studies have suggested that the role of EMT is important in the aggressiveness and metastasis of TNBC. It is also known to play an important role in the formation of tumors in most invasive cancer. The main functions of EMT, such as down-regulation of E-cadherin and up-regulation of MMP, are known to be regulated by transcription factors including Snail, Slug and ZEB1.

Methods

For investigation of ELF3 ability in TNBC, we performed a series of assays; western blot, wound healing, invasion, soft-agar colony formation, flow cytometry, anoikis, CAM and immunofluorescence assays.

Results

In this study, we found that ELF3, an ETS transcription factor, was expressed low and high in mesenchymal and epithelial type of TNBC cell lines, respectively. Remarkably, overexpressed ELF3 in the highly invasive TNBC cell lines, MDA-MB-231 and BT549, suppressed EMT by attenuating the expression of several EMT-associated proteins (Vimentin, Slug and MMPs). Moreover, ELF3 overexpression reduced the tumor growth of BT549 in chick embryo chorioallantoic membrane (CAM) model.

Conclusions

Although high ELF3 expression has been known to be associated with tumorigenesis of other breast cancer types, overexpression of ELF3 in TNBC suppressed the metastatic potential of invasive TNBC cells. Our results suggest the important role for ELF3 in metastasis of TNBC.

Legal entity responsible for the study

Ewha Womans University

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

In India, breast cancer is the second most common malignant condition among women. It is hereditary in 10% of cases, the majority related to mutations in the BRCA1 and BRCA2 genes. The presence of BRCA germline mutations in breast/ovarian carcinomas has been shown to have prognostic and therapeutic significance. Identification of tumours with BRCA defects has therapeutic and prognostic implications. Our objective was to assess whether immunohistochemical analysis (IHC) for BRCA is an effective method for the detection of BRCA dysfunction in hereditary breast carcinoma or not.

Methods

We have selected 231 patients for BRCA1/2 mutation detection during Aug.2010 to Oct.2015 from the breast cancer patients attended our hospital, NCRI. After taking written consent 4-5ml peripheral blood and/or operated tissue (where possible) were collected from BC patients. BRCA1/2 mutations were identified by ARMS-PCR, DNA sequencing and whole genome sequencing. We performed IHC staining with BRCA1 and BRCA2 antibody to distinguish tumour status between patients according to their indication of BRCA1 or BRCA2 mutation.

Results

Average age of the patients was 45.87±1.57 yrs. BRCA1/2 mutations were identified in 24 (10.38%) patientsthrough above mentioned methods. Tumour samples fromnine BRCA positive cases and 15BRCA negative cases were chosen for investigation of IHC. Out of 9 samples with BRCA mutations, 7were BRCA immunostainingnegative, with absence of nuclear or cytoplasmic staining. On the otherhand, from the 15 patients negative for mutations in both genes, 12 were positive for BRCA1immunostaining with a clear nuclear immunoreactivity in tumour cells. From ROCcurve analysis, it was found that IHC negativity (area- 0.211, CI: 0.011-0.411) isassociated (p = 0.02) with BRCA positivity.

Conclusions

In conclusion, we observed a high specificity for the prediction of BRCA1/2 carriers withimmunohistochemistry using BRCA antibody. Validation of this assay, using a larger sample, will allow using immunohistochemistry to decide which high-risk patients should be screenedfirst for the BRCA mutation gene.

Clinical trial identification

NA

Legal entity responsible for the study

Netaji Suibhas Chandra Bose Cancer Research Institue

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

In this study, we observe the patterns initial palliative treatment for premenopausal patients with HR-positive/HER2-negative MBC and determine if non-adherence to clinical guidelines are associated with worse clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) in the South Korean population.

Methods

A retrospective review was performed for premenopausal patients diagnosed with HR-positive MBC between October 1997 and May 2016 who received palliative systemic treatments at a large tertiary medical center. Survival outcomes were analyzed according to the palliative treatment received prior to disease progression.

Results

The review identified a total of 272 premenopausal patients with HR-positive/HER2-negative MBC. The patients were young (median age, 39 years), as per the premenopausal criteria. Chemotherapy alone was first-line palliative treatment in 78 patients, with endocrine therapy as the initial treatment in 133 patients. In 57 patients, the first line treatment was switched from chemotherapy to endocrine treatment prior to any disease progression. Both progression free survival and overall survival were significantly longer for chemotherapy-endocrine therapy (median PFS 18.2 months and OS 85.2 months) than for chemotherapy-alone (median PFS 12.6 months and OS 45.5 months) or endocrine therapy-alone (median PFS 7.0 months and OS 57.3 months) (all P values < 0.01). In multivariate analysis, chemotherapy-endocrine therapy was an independent predictive value for improved PFS and OS (hazard ratio [HR] 0.33, 95% CI 0.20-0.52, P < 0.001; HR 0.38, 95% CI 0.19-0.73, P = 0.004).

Conclusions

In our study population, chemotherapy alone was not objectively inferior to endocrine therapy as the initial palliative treatment. In addition, chemotherapy followed by endocrine therapy was associated with objective higher response rate than endocrine therapy alone. Further studies should explore the relationship between non-adherent treatment patterns and patient outcomes across the largely premenopausal breast cancer populations across Asian countries.

Legal entity responsible for the study

Prof. Yeon Hee Park

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (mBC) is an important consideration for their subsequent use in clinical practice. In a systematic literature review, we evaluated differences in outcome regarding progression free survival (PFS), time to progression (TTP), overall survival (OS) and visceral versus non-visceral disease. The impact of HER2- and hormone receptor-status was also considered.

Methods

A systematic literature search (6362 hits) in the meta-Database PubMed was performed for the last 20 years. 257 studies (n = 126,291) were included for further analysis. 69 studies had published data for visceral vs non visceral disease including phase III trials. Out of these 69 studies we selected n = 16 studies (n = 13,083) which looked at the endpoints mentioned above. In order to achieve comparability, we extracted the information of hazard ratios (HR), confidence intervals (CI) and times in weeks (if available) for PFS, TTP, OS of the entire study population, which was divided into three groups: HER2-positive, HER2-negative, unknown HER2 status.

Results

No statistically significant difference in treatment response was found in mBC patients looking at HRs and CIs. Relevant, yet not statistically significant differences were found in the specific response of visceral metastases to modern combination therapies, especially in HER2-positive breast cancer: There was a benefit regarding OS using lapatinib combined with trastuzumab or trastuzumab and docetaxel combined with pertuzumab. Additionally, in two chemotherapy trials, there was a numerical difference between therapy response in visceral vs. non-visceral metastases regarding PFS in the unknown HER2 group, and regarding OS in the HER2 negative group.

Conclusions

In the subgroup analyses, we did not find any significant differences in response rates for visceral vs. non-visceral metastasis. There seems to be a beneficial effect of combination therapies regarding OS in visceral disease. At the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in mBC.

Legal entity responsible for the study

Tahir Mehmood

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Eribulin mesylate (ERI) demonstrated a survival benefit in patients with locally recurrent or metastatic breast cancer who previously received 2 or more chemotherapy regimens. Recently, we conducted Phase II study about the efficacy of ERI with trastuzumab (ERI+TRA) as late-line therapy for locally advanced or metastatic HER2-positive breast cancer (UMIN000012350), and reported that objective response rate (ORR) and median progression-free survival (mPFS) were 17% and 4.6 months. However, some patients who received prior pertuzumab (PER) and/or T-DM1 were enrolled in that study, there are limited data on the efficacy of ERI+TRA in those patients. The aim of this study was to assess the efficacy of this combination therapy based on prior PER and/or T-DM1 use.

Methods

In primary phase II study, patients with locally advanced or metastatic HER2 positive breast cancer who previously received at least one chemotherapeutic regimen, received ERI at 1.4 mg/m² intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial TRA dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of TRA on day 1 of each subsequent cycle. ORR, clinical benefit rate (CBR) and PFS were assessed in patients who had and had not received prior PER and/or T-DM1.

Results

Thirty-six patients (median age: 60.5 years) received ERI+TRA. 69.4% (n = 25) had previously treated with prior PER and/or T-DM1, defined as ‘prior’ patients. Remaining 30.6% (n = 11) without both agents were defined as ‘non-prior’ patients. In prior patients compared with non-prior patients, median number of prior treatment regimens was 4 (range, 1‐8) versus 3 (range, 1-7), respectively; ORR was 12.0% versus 27.3%, respectively; CBR was 24.0% versus 54.5%, respectively; mPFS was 4.3 versus 9.7 months, respectively.

Conclusions

ERI+TRA demonstrated lower efficacy than in non-prior patients, but CBR and PFS were 24.0% and 4.3 months, which was considered to be a clinically relevant treatment option in patients who received prior PER and/or T-DM1.

Clinical trial identification

UMIN000012350.

Legal entity responsible for the study

Nagoya Surgical Oncology Group

Funding

Eisai

Disclosure

All authors have declared no conflicts of interest.

Background

Varlitinib, a tyrosine kinase inhibitor of the ErbB family (EGFR, HER2 and HER4), showed anti-tumor activity in trastuzumab-resistant models and in patients with trastuzumab-resistant, chemotherapy-refractory MBC in a phase 1 study. This study compared the efficacy and safety of varlitinib plus capecitabine (VC) versus lapatinib plus capecitabine (LC) in HER2⁺ MBC patients who failed prior trastuzumab therapy.

Methods

The primary objective was to assess percentage change in tumor size at week 12. Objective response rate (ORR), safety and drug exposure were also assessed. Patients who received at least one dose of study treatment were included in primary analysis. Sensitivity analysis for primary objective and ORR were performed in patients who remained on study for more than 30 days.

Results

From Dec 2014 to Aug 2016, 24 patients were randomized to the VC arm (400mg BID) and 26 to the LC arm (1250mg QD) in 16 sites in 6 countries. Percentage of tumor size reduction was numerically higher in VC than LC (-31.00% vs. -19.37%, one-sided p = 0.132). ORR in the VC arm (40.9%) was similar to LC arm (45.5%), p = 1.000. Sensitivity analysis showed numerically superior ORR and statistically significant higher reduction of tumor size in VC compared to LC (60% vs. 45.5%, p = 0.508; mean, -34.6% vs.-19.4%, one-sided p = 0.075) All patients had at least 1 AE. Severe AE(s) were observed in 13 patients (54.2%) in the VC arm and 11(42.3%) in the LC arm. The most common AE was diarrhea (66.7%) in the VC arm and were diarrhea and palmar-plantar erythrodysaesthesia syndrome (both 50%) in the LC arm. Median intended exposure and percentage of intended dose were lower in the VC arm (115.5 days, 74.6%) indicating more frequent dose interruption, dose reduction and treatment discontinuation than the LC arm (135.0 days, 99.05%).

Conclusions

Sensitivity analysis showed greater tumor size reduction and improved ORR for VC arm when the combination was administrated for more than 30 days. Reduced intended exposure and dose intensity for the VC arm suggests a dose reduction of varlitinib may be considered when combined with capecitabine for the 2nd line treatment of HER2⁺ MBC.

Clinical trial identification

NCT02338245.

Legal entity responsible for the study

ASLAN pharmaceuticals

Funding

ASLAN pharmaceuticals

Disclosure

All authors have declared no conflicts of interest.

Background

The efficacy and tolerability of palbociclib (P) + endocrine therapy (ET) in ABC patients (pts) was previously established; here, we report results in the Asia-Pacific (AP) region (Australia, Japan, Korea, Taiwan).

Methods

In PALOMA-2, postmenopausal women untreated for their HR+/HER2- ABC were randomized 2:1 to P (125 mg/d [3/1 schedule]) + letrozole (L; 2.5 mg/d) or placebo (PB)+L. In PALOMA-3, women of any menopausal status with HR+/HER2- ABC, whose disease had progressed after previous ET, were randomized 2:1 to P + fulvestrant (F; 500 mg) or PB+F.

Results

Of 666 PALOMA-2 pts, 92 (14%) were from the AP region (P+L, 64; PB+L, 28). Baseline characteristics: median age (61 y) younger than overall population; white (20%), Asian (79%); ≥2 disease sites (70%); visceral disease (59%); prior (neo)adjuvant ET (64%); disease-free interval >12 months since prior (neo)adjuvant therapy (58%). Median PFS (mPFS): 22 mo (95% CI, 19-26) for P+L vs 14 mo (7-22) for PB+L (HR, 0.49; 1-sided P=0.007). All-grade treatment-emergent adverse events (TEAEs) (P+L/PB+L) occurred in 100%/96% of pts; the most common AE in the P+L arm was neutropenia (91%). 55% of P+L pts required a dose reduction due to AEs. Of 521 PALOMA-3 pts, 114 (22%) were from the AP region (P+F, 78; PB+F, 36). Baseline characteristics: younger (median age 53 y) and more premenopausal pts (38%) vs overall population; white (23%), Asian (75%); ≥2 disease sites (66%); visceral disease (57%); prior ET (100%); prior chemotherapy for ABC (70%). mPFS: 13 mo (95% CI, 9-16) for P+F vs 6 (4-9) for PB+F (HR, 0.51; 1-sided P=0.002). All-grade TEAEs (P+F/PB+F) occurred in 100%/92% of pts; the most common AE in the P+F arm was neutropenia (95%). 51% of P+F pts required a dose reduction due to AEs.

Conclusions

Because PALOMA-2 only enrolled postmenopausal pts and percentages of premenopausal pts in AP vs other regions was higher, the proportion of AP pts was higher in PALOMA-3 vs -2. P+ET showed clinically meaningful improvement in mPFS vs PB+ET and a tolerable safety profile in AP pts with HR+/HER2- ABC in the 1^st-line and later-lines of therapy, regardless of menopausal status.

Clinical trial identification

Pfizer (NCT01740427; NCT01942135).

Legal entity responsible for the study

Pfizer Inc

Funding

Pfizer Inc.

Disclosure

S-A. Im: Consulting or advisory role for AstraZeneca, Novartis, Hanmi Corp, and Spectrum, N. Masuda: Honoraria from Chugai and AstraZeneca, K. Inoue: Research funding from Pfizer, Lilly, Chugai, Daiichi-Sankyo, Taiho, MSD, Parexel (Puma), S-B. Kim: Research funding from Novartis, Sanofi-Aventis, Kyowa-Kirin Inc, and Dongkook Pharma Co., Ltd. A. Redfern: Advisory board for Pfizer Australia, J. Lombard: Honoraria from Roche and AstraZeneca, D. Lu, K. Puyana Theall, E.G. Gauthier: Employee and owns stock in Pfizer, H. Mukai: Honoraria from AstraZeneca, Eisai, Novartis Pharma and Taiho Pharmaceutical, and received research funds from Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Sanofi

All other authors have declared no conflicts of interest.

Background

MONALEESASIA is an ongoing Phase Ib dose-escalation/-expansion study evaluating RIB + LET in a subset of Asian pts from Hong Kong and Singapore with HR+, HER2–ABC.

Methods

Postmenopausal pts from Hong Kong and Singapore with HR+, HER2– ABC and no prior systemic therapy for ABC received RIB (400 or 600 mg/day; 3-weeks-on/1-week-off) + LET (2.5 mg/day; continuous). Dose escalation used a Bayesian Logistic Regression Model with overdose control. The primary endpoint was to determine the maximum tolerated dose (MTD)/recommended Phase II dose (RP2D); secondary endpoints included safety and pharmacokinetic (PK) profile. Blood samples for PK non-compartmental analysis were collected on Days 1 and 21 of Cycle 1 from pre-dose to 24 h post-dose.

Results

At data cut-off (Jan 16, 2017), 26 pts were enrolled (RIB 400 mg: n = 6; 600 mg: n = 20). One dose-limiting toxicity was observed at 600 mg (Grade 3 increased alanine transaminase [ALT]); the MTD/RP2D was RIB 600 mg/day (3-weeks-on/1-week-off) + LET 2.5 mg/day (continuous). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 4/6 pts at 400 mg and 17/20 pts at 600 mg during the dose-escalation and -expansion parts. The most common Grade 3/4 TRAEs (≥20% in either cohort; 400 mg vs 600 mg) were decreased neutrophil count (n = 3 vs n = 7), neutropenia (n = 1 vs n = 6), increased ALT (n = 1 vs n = 4), and increased aspartate transaminase (n = 0 vs n = 4). After a single dose (Cycle 1 Day 1) and at steady state (Cycle 1 Day 21), absorption of both RIB and LET was rapid (Table); increases in RIB exposure were dose dependent.

Conclusions

The MTD/RP2D was declared as RIB 600 mg/day (3-weeks-on/1-week-off) + LET 2.5 mg/day (continuous) in Asian pts from Hong Kong and Singapore with HR+, HER2– ABC. Preliminary safety and PK data are consistent with prior observations in non-Asian pts.

Clinical trial identification

CLEE011A2115C/NCT02333370.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

Y-S. Yap: Received honoraria and provided consultancy for Novartis. Y. Ito: Yoshinori Ito reports grants from MSD, AstraZeneca, Novartis, Parexel, Chugai, and Lilly. O. Bornstein: Orna Bornstein is an employee of Novartis Pharmaceuticals Corporation. Y. Han: Yu Han is an employee at Novartis Pharmaceuticals Corporation. T. Samant: Tanay Samant is an employee of Novartis Pharmaceuticals Corporation and owns stocks/shares in Novartis Pharmaceuticals Corporation. X. Liu: Xiaochun Liu is an employee of Novartis Pharmaceuticals Corporation and owns stocks in Novartis Pharmaceuticals Corporation. J. Chiu: Dr. Chiu served on advisory boards for Novartis and Pfizer.Table: 94O

Summary of RIB and LET PK profiles

Background

Results from the primary analysis of the open-label, single-arm, phase 2 study BOLERO-4 demonstrated that first-line (1L) EVE + LET was an effective combination with a manageable safety profile in postmenopausal patients with ER+ HER2− ABC. Here, we present results from a predefined subgroup analysis of 1L progression-free survival (PFS) and safety by race (Asian versus non-Asian).

Methods

Patients received EVE 10 mg/day + LET 2.5 mg/day until disease progression, unacceptable toxicity, or withdrawal of consent. 1L PFS per local investigator assessment was analyzed overall on the full analysis set (FAS; primary endpoint) and by patient subgroup. This study was not designed to use the SWISH protocol for prevention for stomatitis.

Results

At the data cutoff (December 17, 2016), 44 Asian and 158 non-Asian (Caucasian 72%; Black 4%; Pacific Islander <1%; other 2%) patients had a median PFS and 18- and 24-month KM estimated PFS rates similar to the FAS (Table). In general, all grade adverse events (AEs), regardless of causality or severity, were more common among Asian patients versus non-Asians and the overall population, particularly for stomatitis, weight decreased, anemia, hyperglycemia, decreased appetite, rash and nasopharyngitis. AEs were mostly grade 1–2 in severity and anemia was the most common grade 3–4 AE among both Asian (20%) and non-Asian (8%) patients.Table: 92O

Conclusions

Results from this predefined subgroup analysis were consistent with previously reported BOLERO-4 data, showing that 1L EVE + LET offers clinical benefits irrespective of patient race, with no new safety signals reported. Although some AEs were more common among Asian patients versus non-Asians and the overall population, they were mostly grade 1–2 in severity.

Clinical trial identification

NCT01698918 EudraCT Number (EU number) 2012-003065-17

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation

Funding

Novartis Pharmaceuticals Corporation

Disclosure

T. Toyama: Research funding from Eisai, Chugai, Novartis, Nippon Kayaku, Kyowa Hakko Kirin, Daiichi-Sankyo, Takeda, J. Jeong: Research funding from Dong-A, Boryung, LG Life Sciences, Antigen; Honoraria from Roche, Alvogen, Novartis, Pfizer, Covidien, V. Sriuranpong: Honoraria from Novartis, Roche, MSD, Sanofi, Eisai, AstraZeneca, H. Iwase: Research funding from AstraZeneca, Chugai-Roche, Taiho, Daiichi-Sankyo, Novartis, Pfizer, Kyowa Hakko-Kirin, Eisai; Honoraria from AstraZeneca, Novartis, Takeda, Chugai-Roche. C. Arce: Novartis employee, A. Ridolfi: Novartis Pharma SAS employee, C. Lin: Novartis employee and stocks, M. Royce: Research funding from Novartis; Consultant for Celltrion, BCI; Honoraria from Novartis, Syndax, F. Cardoso: Research funding for clinical trials by institution; consultant for Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GSK, MacroGenics, Merck, Merus BV, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Teva

All other authors have declared no conflicts of interest.

Background

As treatment outcomes for mTNBC are poor, new treatment options are needed. We present a subgroup analysis for the safety and antitumor activity of pembrolizumab (PEM) as a therapy for Japanese patients (pts) with mTNBC in Cohorts A and B of KEYNOTE 086.

Methods

Pts with centrally confirmed mTNBC, at least one systemic treatment (Cohort A) or no prior systemic therapy (Cohort B) for metastatic disease, ECOG PS 0-1, and regardless of tumor PD-L1 expression (Cohort A) or with a tumor PD-L1 combined positive score (CPS) ≥1% (Cohort B), received PEM 200 mg IV every 3 weeks (wk) for 24 months (m) or until disease progression, intolerable toxicity, or investigator or patient (pt) decision. Tumor imaging was performed Q9W for 12 m and Q12W thereafter. Clinically stable pts with PD could remain on PEM until PD was confirmed on subsequent assessment. Primary endpoints were ORR (RECIST, central review) in Cohort A and safety in Cohorts A and B. Secondary were ORR in Cohort B, disease control rate (CR + PR + SD ≥ 24 wk), PFS and OS in Cohorts A and B.

Results

Of 20 pts in Cohort A, 12 had PD-L1 (+) tumors and 8 had PD-L1 (-) tumors. The median age was 53.5 y, 11 pts had elevated LDH and 13 pts had visceral metastases. Of 9 pts in Cohort B, median age was 38.0 y, 1 pt had elevated LDH, 5 pts had visceral metastases. As of Nov 10, 2016, the best overall response was PR in 1 pt and SD in 2 pts in Cohort A, and CR in 1 pt and SD in 2 pts in Cohort B. Median PFS was 2.0 m (95% CI, 1.7 – 2.1) in Cohort A, and 2.1 m (95% CI, 1.6 – 4.2) in Cohort B. Median OS was 8.3 m (95% CI, 4.6 – 10.3) in Cohort A, and was not reached in Cohort B. Drug-related AEs (DRAEs) occurred in 20 pts (67.0%) in Cohorts A and B; the most common DRAEs were pruritus (4 pts), fatigue, pyrexia, anemia, rash, and diarrhea (3 pts each). Grade (Gr) 3-4 DRAEs were diarrhea, nausea, and bacteraemia (1 pt each), all in Cohort A. Infusion reaction (1 pt, Gr 2), interstitial lung disease (1 pt, Gr 1), hypersensitivity (1 pt, Gr 2) and hyperthyroidism (1 pt, Gr 1) were seen as irAE. No pts died or discontinued PEM due to AEs.

Conclusions

Data from 29 Japanese pts in Cohorts A and B suggest that PEM monotherapy has a well tolerated safety profile and anti-tumor activity which are similar to those reported in the overall populations.

Clinical trial identification

NCT02447003.

Legal entity responsible for the study

Merck & Co., Inc., Kenilworth, NJ, USA

Funding

Merck & Co., Inc., Kenilworth, NJ, USA

Disclosure

H. Mukai: Received personal fees as honoraria from AstraZeneca, Novartis Pharma, Daiichi Sankyo, and Taiho Pharmaceutical, and received research funds from Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and MSD.K.K. N. Masuda: Honoraria: Chugai, Astrazeneca. H. Ishiguro: Advisory board: MSD.K.K. T. Shimamoto, K. Yamamoto: Employees of MSD.K.K. Y. Ding, G. Aktan, V. Karantza: Employees of Merck

All other authors have declared no conflicts of interest.