Background

Irreversible EGFR-TKI monotherapies showed only moderate efficacy after AR to reversible EGFR-TKIs. Preclinical studies suggested that addition of Bev to EGFR-TKIs could overcome AR.

Methods

ECOG PS 0-2 patients (pts) with EGFR-mutant NSCLC after AR to EGFR-TKIs were enrolled at any lines. Rebiopsy was essential to confirm T790M status after AR. Afa was prescribed at 30 mg, and Bev administered at 15 mg/kg tri-weekly until progression. Primary endpoint was response rate (RR).

Results

Between October 2014 and May 2017, 32 eligible pts were evaluated. Median age was 66 (range, 48-86). Twenty-one (66%) pts were female, and 21 (66%) were never smoker. Mutation subtypes were 20 (63%) Del-19, 11 (34%) L858R, and 1 (3%) L861Q. T790M was detected in 14 (44%) pts. Median number of prior regimens was 4 (range, 1-10). First prior TKIs were 19 (60%) gefitinib, 10 (31%) erlotinib or 3 (9%) Afa. Six pts obtained partial response and 23 stable disease, resulting in RR of 18.8% (95% confidence interval [CI], 7.2-36.4%) and disease control rate of 90.7% (95% CI, 75.0-98.0%). Median progression-free survival (PFS) and overall survival were 6.3 (95% CI, 3.9-8.7) months and not reached, respectively. RR and median PFS of T790M+ vs. T790M- were 14.3% vs. 22.2% (p = 0.2094) and 6.3 vs. 7.1 months (p = 0.7910), respectively. RR and median PFS of Del-19 vs. L858R were 20.0% vs. 11.1% (p = 0.9024) and 6.3 vs. 5.1 months (p = 0.7777), respectively. Afa dosage was reduced to 20 mg in 17 (53%) pts and increased to 40 mg in 2 (6%) pts. Median number of Bev administrations was 6 (range, 2-14). Bev was interrupted in 5 (16%) pts. Adverse events ≥grade 3 (incidence ≥5%): anemia (6%); mucositis (6%); anorexia (6%); paronychia (25%); hypertension (41%); and proteinuria (19%) were observed. There were no treatment-related deaths, interstitial lung disease, nor Bev-associated severe bleedings.

Conclusions

Afa + Bev demonstrated clinical efficacy and safety after AR to EGFR-TKIs. It could be a therapeutic salvage option for NSCLC with AR to EGFR-TKIs, especially for T790M- populations whose therapeutic options are limited.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

We aimed to assess the therapeutic yield of R0 gastrectomy with adjuvant chemotherapy and evaluate the predictive risk factors of overall recurrence

Methods

We designed the retrospective cohort study with the patients who were diagnosed as advanced gastric cancer and treated with R0 gastrectomy and adjuvant combination chemotherapy at the Catholic University of Korea, from January 2007 to January 2012. For the follow-up 5 years, recurrent events were checked. Between recurrence and non-recurrence, the variable factors including tumor markers were evaluated according to nodal involvement. A total of 890 patients with gastric cancer had operations. We analyzed variable factors predictive of overall recurrence according to the lymph node status.

Results

Finally, 130 patients with advanced gastric cancer had R0 gastrectomy and completed 6 cycle adjuvant chemotherapy. The total recurrence rate was 36.9% (48/130). In lymph node positive group, the numbers of metastatic lymph node and dissected lymph nodes were independent risk factors. When lymph node ratio (LNR) was defined as ratio between metastatic lymph nodes and total dissected lymph nodes, the recurrence could be predicted with high sensitivity, as shown by the receiver operating characteristic curve (AUC, 0.74; 95% confidence interval, 0.65 to 0.83). In lymph node negative group, baseline CA19-9 level was a risk factor for the recurrence.

Conclusions

Despite the adjuvant chemotherapy, recurrent gastric cancers occurred in a considerable number of patients. The more potent adjuvant chemo-regimen should be considered in patients with high LNR and high level of CA19-9.

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Breast cancer in women is an important cause of cancer‐related mortality. MicroRNA‐200c (miR‐200) is important in the epithelial to mesenchymal transition (EMT) and plays a major role in breast cancer metastasis. The present study focused on investigating the prognostic importance of cell-free miR‐200c expression in breast cancer patients.

Methods

A total of 75 histopathologically confirmed newly diagnosed breast cancer female subjects as well as 75 healthy controls were included. Blood samples of subjects were collected in serum vial and total RNA from serum was isolated by using Trizol reagent. Total RNA was polyadenylated and reverse transcribed into cDNA. Expression level of miR‐200c was detected by using miRNA qRT‐PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Levels of miRNA expression was compared with distinct clinicopathological features. Total follow up period was 41 months and mean follow up time was 28 months. Kaplan Meier survival testing was performed to calculate the overall survival of breast cancer patients. The study was ethically approved by Institutional Ethics Committee, Maulana Azad Medical College, New Delhi.

Results

The overall relative fold increase of miR‐200c expression was 8.80-fold in breast cancer patients compared to the healthy controls. Level of cell free miR‐200c expression was compared with distinct clinicopathological features. There was a significant association was found between miR‐200c expression with TNM stage (p = <0.0001), histological grade (p= 0.006), lymph node status (p= 0.006) and distant metastasis (p= 0.006) in breast cancer patients. ROC curves for prognosis yielded significant AUC values for early vs advanced stage, histological grade, lymph node involvement, and distant metastasis. There was a significant association (p= 0.006) found between overall survival and expression of miR‐200c in breast cancer patients.

Conclusions

The study revealed that the cell-free miR‐200c overexpression may be a useful, noninvasive, prognostic and predictive biomarker for breast cancer patients. A large pool study would be necessary to confirm our findings.

Clinical trial identification

NA

Legal entity responsible for the study

Dr Alpana Saxena

Funding

None

Disclosure

All 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

S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small-cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown.

Methods

The patient inclusion criteria were previously untreated advanced NSCLC, wild-type EGFR, aged 70 years or more, and a PS of 0–2. The patients received oral S-1 (40 mg/m², twice daily) for 2 weeks and carboplatin (AUC 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40 mg/m², twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated.

Results

Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70–89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6–46.0) and the DCR 57.6% (95% CI: 40.7–74.4). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia (27.3%). There was one treatmentrelated death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134 days (95% CI: 79–173) and 479 days (95% CI: 250–571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P < 0.01).

Conclusions

This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option.

Clinical trial identification

University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): UMIN000009345.

Legal entity responsible for the study

Okayama Lung Cancer Study Group (OLCSG)

Funding

None

Disclosure

A. Bessho: Speakers Bureau : AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. KYORIN Pharmaceutical Co., Ltd. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co ., Ltd. S. Kuyama: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan Chugai Pharmaceutical Co., Ltd. Nippon Boehringer Ingelheim Co ., Ltd. D. Harada: Speakers Bureau ONO PHARMACEUTICAL CO., LTD. Bristol-Myers Squibb Company Yakult Honsha Co., Ltd. Kyowa Hakko Kirin Co., Ltd. N. Nogami: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd. N. Fujimoto: Speakers bureaus ONO PHARMACEUTICAL CO., LTD. MSD K.K. K. Hotta: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co ., Ltd. Research Funding MSD, Chugai, Lilly, ONO, BMS, Novartis, N. Takigawa: Reseach funding: Boehringer Ingelheim, Chugai Pharma, Pfizer, AstraZeneca, Taiho Pharmaceutical, Kyowa-Hakko Kirin, Nihonkayaku, Ono Pharmaceutical Honoraria: Chugai Pharma, Pfizer, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Kyowa-Hakko Kirin, Daiichi-Sankyo, Eisai, Ono Pharmaceutical, MSD, Eli-Lilly Japan, K. Kiura: Speakers Bureau AstraZeneca K.K. Bristol-Myers Squibb Japan ONO PHARMACEUTICAL CO., LTD. Chugai Pharmaceutical Co., Ltd. TAIHO PHARMACEUTICAL CO., LTD. Pfizer Japan Inc. Eli Lilly Japan K.K. Nippon Boehringer Ingelheim Co., Ltd.

All other authors have declared no conflicts of interest.

Background

The incidence of esophageal cancer is rising worldwide. The objective of this study is to find out the epidemiological features, treatments received and outcomes of patients with esophageal cancer who came for consultation to Medical Oncology Department, Yangon General Hospital (YGH), one of the tertiary hospitals in Myanmar.

Methods

Data of all patients with esophageal cancer who came to Medical Oncology Department, YGH in 2015 and 2016 were collected and their clinic charts were reviewed retrospectively. This is a descriptive study.

Results

A total of 101 patients were identified; male 81 (80%) and female 20 (20%) with a male to female ratio of 4:1. Median age is 60 years (range 32-81). Risk factors (smoking, betal nut chewing and alcohol drinking) can be assessed only in (18%). The most common symptom present was dysphagia (83%). 99 (98%) patients were diagnosed by OGDS; 51 (50%) patients involved middle third of esophagus. CT scan could be done only in 26 patients (26%). Only 12 (12%) patients had definitive surgery (esophagectomy). The majority of patients (76%) were stage III. (19%) were stage IV where liver was the common site for metastases. Squamous Cell Carcinoma was the most common histology (69%) followed by Adenocarcinoma (23%). 66 patients received 5FU based chemotherapy; but only 34 patients completed 4-6 cycles of chemotherapy. 19 patients received radiotherapy (RT) to tumor sites; 4 patients had adjuvant RT after definitive surgery and in 1 patient concurrently with chemotherapy. Palliative RT was given to 2 patients for brain metastasis and bone metastasis. (34%) failed to come back after first visit, (46%) defaulted during chemotherapy and (3%) expired during chemotherapy. 18 (18%) patients were progression free during follow up period (6-12 months).

Conclusions

On reviewing the patients with esophageal cancer, early detection is very important. To upgrade our cancer care, not only to improve public awareness but also upgrade the diagnostic facilities and better clinical documentations are essential.

Legal entity responsible for the study

Yangon General Hospital

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

Post mastectomy radiotherapy (PMRT) reduces loco-regional recurrence (LRR) and improves overall survival. There is international consensus to recommend PMRT for patients with tumour size more than 5 cm, tumour invasion of the skin, pectoral muscle or chest wall and patients with > 4 positive lymph nodes. However, the role of PMRT for patients with T1, T2 disease with 1–3 positive LN is still controversial. The side effects of radiotherapy and its associated morbidity have to be considered in the risk benefit ratio, thus difficult to arrive at consensus in early breast cancer.

Methods

101 patients treated between 2012 to 2015 were studied retrospectively, The inclusion criteria for this analysis were: (1) Female patients with unilateral breast cancer and no distant metastasis at initial diagnosis who underwent mastectomy and axillary lymph node dissection; (2) postoperative pathology indicated T1–2 and 1–3 positive axillary lymph nodes (T1–2N1M0) disease, at least 10 lymph nodes removed by axillary dissection; (3) complete surgical resection of the tumor and negative margins; (4) complete estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor family 2 (Her2) status; (5) No neoadjuvant chemotherapy was administered before surgery and endocrine therapy was performed based on the hormone receptor status. In order to study the research questions, we formulated hypotheses as follows,1. Radiotherapy does not have any impact on recurrence post mastectomy.2. There is no influence of Peri nodal extention on recurrence. The above hypotheses were tested using chi-square test.

Results

Recurrences were obtained in 9 amongst radiotherapy and without radiotherapy in 16. When chi square was applied, the value was highly significant. Hence our hypothesis was rejected. Also in case of PNE with recurrence and radiotherapy, 8 had PNE with radiotherapy and recurrence and 27 had no recurrence, p value was 0.013% hence highly significant.

Conclusions

Radiotherapy should be strongly considered in patients with 1-3 nodes post mastectomy as it decreases the chances of recurrence.

Legal entity responsible for the study

GCRI Ahmedabad, India

Funding

None

Disclosure

All authors have declared no conflicts of interest.

Background

A recent Phase I study of metronomic oral vinorelbine (60mg, 90mg and 120mg) per week and 200mg BID sorafenib in Asian NSCLC patients performed by our group showed that the combination of 60mg/week vinorelbine and 200mg BID sorafenib correlated with better survival and response. We herein report the pharmacokinetics (PK) profile of metronomic vinorelbine at these three doses in combination with 200mg BID sorafenib in Asian NSCLC patients to better understand the pharmacology of this low dose combination treatment.

Methods

Thirty-five NSCLC patients were randomly allocated into two treatment schedules S1 (N = 19) and S2 (N = 16) and sub-grouped to receive either oral vinorelbine at three dose levels on Day 1 followed by 200mg sorafenib BID on Day 17 (S1) and vice-versa (S2). PK analysis of samples collected at steady-state on Days 15 and 29 from each group were quantified using LC-MS/MS. PK parameters were derived using non-compartmental analysis. Statistical analyses were performed on GraphPad Prism 6.0c.

Results

Higher exposure of vinorelbine as determined by these PK parameters (average vinorelbine concentrations (C_av), area under the plasma-concentration curve (AUC_0-∞) and vinorelbine clearance (CL/F)) was observed in 60mg/week cohort compared to that of 90mg/week group in S1 on Day 15. [60mg/week vs 90mg/week respectively C_av: 2.62 ng/mL vs 0.57 ng/mL, P=0.016; AUC_0-∞: 277.7 h.ng/mL vs 41.2 h.ng/mL, P=0.06; CL/F: 158.77 L/h vs 1094.0 L/h, P=0.016]. Similar trends in C_av, AUC_0-∞ and CL/F were also observed from steady-state samples collected at Day 29 in both schedules; probably suggesting a lack of drug-drug interactions between vinorelbine and sorafenib. Due to insufficient sampling collection, analysis could not be performed for the 120mg/week cohort. No significant changes in sorafenib PK parameters were discernible in either S1 or S2.

Conclusions

This pilot study illustrates that 60mg/week vinorelbine confers a more superior PK profile and improved clinical response compared to 90mg/week or 120mg/week. Future studies should investigate the combined therapeutic effect of 60mg/week vinorelbine and 200mg BID sorafenib in a Phase II efficacy trial.

Legal entity responsible for the study

National Cancer Centre Singapore

Funding

National Medical Research Council

Disclosure

All authors have declared no conflicts of interest.

Background

There is no study till date determining the spectrum of adverse events of pazopanib in Indian patients with advanced sarcoma.

Methods

We conducted a retrospective study by analyzing case records of metastatic sarcoma patients treated with pazopanib from January 2016 to July 2017 who received pazopanib in sarcoma medical oncology clinic. Our practice in clinic is to start on 400mg dose and then escalate to 800mg. Toxicity was assessed according to CTCAE v.4.03 criteria. SPSS version 17 was used for statistical evaluation.

Results

A total of 28 patients received pazopanib out of which a majority (60%) received it after 2 lines of therapy. Median age was 40 years (range 18 years to 75) and majority (53%) of patients were males. Most common type of sarcoma was malignant peripheral nerve sheath tumor (MPNST) and mean duration for pazopanib intake in patients was 4.6 months. Median progression free survival (PFS) was 6 months. Overall response rate (ORR) was 10.7%. In majority of patients (n = 23,82%)dose could not be escalated beyond 400mg due to toxicities, four patients (15%) received 600mg and in only one patient (3%) the dose of pazopanib could be escalated to 800 mg per day. Most common grade 3 and 4 toxicities experienced amongst patients were hand foot skin reaction (23%) and hypertension (19.2%). Other grade 3 and 4 adverse events were LFT derangement (7%), diarrhea (7%), proteinuria (3.8%), thrombocytopenia (3.8%) myalgia (3.8%), and oral mucositis (3.8%).

Conclusions

The spectrum of adverse events in Indian patients at doses lower than recommended is distinctly different from western population. The survival and response data trends are better than that reported in international literature and can be attributed to retrospective nature of this study or a regional variation. However, this unique toxicity profile needs to be validated in prospective studies.

Legal entity responsible for the study

Dr. Sameer Rastogi

Funding

None

Disclosure

All authors have declared no conflicts of interest.