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K. Nakagawa
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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.11 - Phase II Study of Nimotuzumab + Concurrent Chemoradiotherapy (CRT) for Stage III Non-Small Cell Lung Cancer (NSCLC): 5-Year Follow-Up Results (ID 3868)
16:00 - 17:30 | Author(s): K. Nakagawa
- Abstract
- Presentation
Background:
Nimotuzumab, a humanized IgG~1~ monoclonal anti-EGFR antibody, is approved and widely used in patients (pts) with head and neck cancer or malignant glioma in combination with radiotherapy (RT) in several countries. On in-vitro and in-vivo experiments using NSCLC cell lines, nimotuzumab showed a radio-sensitizing effect.
Methods:
This phase II study evaluated the tolerability and efficacy of nimotuzumab in combination with concurrent CRT in pts with unresectable locally advanced NSCLC. All eligible pts received concurrent thoracic RT (60 Gy, 2 Gy/day, 6 weeks from day 1) and 4 cycles of chemotherapy (cisplatin 80 mg/m[2] on day 1, vinorelbine 20 mg/m[2] on days 1 and 8) once every 4 weeks as scheduled. Nimotuzumab (200 mg) was administrated once a week from cycle 1 to 4. The primary endpoint was tolerability in combination with concurrent CRT, which was measured by the percentage of pts who completed 60 Gy of RT within 8 weeks, completed 2 cycles of chemotherapy and received more than 75% of nimotuzumab.
Results:
Of 40 pts enrolled between June 2009 and May 2010, 39 eligible pts received the study treatment. The pts characteristics were as follows: 62 years (median); male/female, 34/5; stage IIIA/B, 21/18; PS0/1, 25/14. Thirty-four pts met the criteria for treatment tolerability, and 38 pts completed 60 Gy of RT within 8 weeks. Infusion reaction, >grade 3 skin rash, >grade 3 radiation pneumonitis, or >grade 4 nonhematological toxicity were not observed. The 3-year and 5-year overall survival rates for the 39 pts were 66.4% and 58.4%, respectively. The median PFS was 16.9 months, and the 5-year PFS rate for pts with squamous cell carcinoma (Sq; n = 16) was 50%, while that for pts with non-squamous cell carcinoma (non-Sq; n = 23) was 13.7%. In terms of the first relapse site, in-field relapse rates were low for both Sq (4/16; 25%) and non-Sq (4/23; 17%). However, the distant relapse rate was significantly higher for non-Sq (15/23; 65%) than that for Sq (4/16; 25%). Cytologic or histologic specimens were examined for the expression of EGFR protein/mutations using the EGFR IHC/FISH methods in 20 pts. EGFR 2+/3+ expression was shown more frequently in sq (8/10) than non-sq (4/10). EGFR mutation was observed in only 2 pts with non-sq.
Conclusion:
Addition of nimotuzumab to the concurrent CRT in this setting was well tolerated with clinical benefit to the patients. The low in field relapse rates may be attributed to the radio-sensitizing effect of nimotuzumab.
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MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
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MA07.03 - Alectinib (ALC) versus Crizotinib (CRZ) in ALK-Positive Non-Small Cell Lung Cancer (ALK+ NSCLC): Primary Results from Phase III Study (J-ALEX) (ID 5597)
11:00 - 12:30 | Author(s): K. Nakagawa
- Abstract
- Presentation
Background:
ALK inhibitors are the standard treatment for ALK+ NSCLC and the comparison between 2 ALK inhibitors will be valuable in determining therapeutic strategy for ALK+ NSCLC patients (pts). We conducted the randomized open-label Phase III trial designed to prove the superior PFS of ALC to CRZ in ALK-inhibitor naïve ALK+ NSCLC.
Methods:
ALK+ NSCLC pts were randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.) and stratified by ECOG PS (0/1 vs 2), treatment line (1[st] vs 2[nd]), and clinical stage (IIIB/IV vs recurrence). Primary endpoint was PFS according to the blinded independent review board. Secondary endpoints included overall survival, objective response rate, and safety. Under an assumption of expected hazard ratio (HR) of 0.643, 164 events were required to have 80% power with 2-sided alpha of 0.05. Three interim analyses (IA) for early stopping due to efficacy were planned after 33%, 50%, and 75% of required PFS events occurred.
Results:
207 pts were enrolled at 41 centers in Japan between November 2013 and August 2015. Independent data monitoring committee recommended the release of study data because the superiority in PFS had been demonstrated for ALC based on second IA. The PFS HR of ALC arm to CRZ arm was 0.34 (99.6826% CI: 0.17-0.70, stratified log-rank p<0.0001). Median PFS was not reached (95% CI: 20.3-Not Reached (NR)) in ALC arm while it was 10.2 months (95%CI: 8.2-12.0) in CRZ arm. ALC demonstrated favorable result of PFS in each sub-group for instance, treatment line (1[st] line: HR = 0.30, ALC: NR vs CRZ: 10.2 months, 2[nd] line: HR = 0.39, ALC: 20.3 months vs CRZ: 8.2 months), brain metastases at baseline (yes: HR = 0.08, ALC: NR vs CRZ: 10.2 months, no: HR = 0.39, ALC: 20.3 moths vs CRZ: 10.0 months) and clinical stage (stage IIIb/IV: HR = 0.31 ALC: 20.3 months vs CRZ: 8.3 months, recurrence: HR = 0.49, ALC: NR vs CRZ: 11.6 months). Grade 3-4 AEs (ALC: 26% vs CRZ: 52%), discontinuation of study drug due to AEs (ALC: 9% vs CRZ: 20%) and dose interruptions due to AEs (ALC: 29% vs CRZ: 74%) occurred with lower rate in the ALC arm. There were no treatment-related deaths in either arm.
Conclusion:
ALC demonstrated prolonged PFS compared with CRZ in all sub-groups with a favorable AE profile representing a potential new standard treatment for 1[st] line ALK+ NSCLC pts.
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MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:R. Perez-Soler, T. Reungwetwattana
- Coordinates: 12/06/2016, 11:00 - 12:30, Lehar 3-4
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MA08.10 - Detection of the T790M Mutation of EGFR in Plasma of Advanced NSCLC Patients with Acquired Resistance to EGFR-TKI (WJOG8014LTR) (ID 5377)
11:00 - 12:30 | Author(s): K. Nakagawa
- Abstract
- Presentation
Background:
NSCLC patients with activating mutations of the EGFR initially respond well to TKIs, but about half such patients develop TKI resistance through acquisition of a secondary T790M mutation. Whereas next-generation EGFR-TKIs have been developed to overcome T790M-mediated resistance, performance of a second tumor biopsy to assess T790M mutation status can be problematic.
Methods:
We developed and evaluated liquid biopsy assays for detection of TKI-sensitizing and T790M mutations of EGFR by droplet digital PCR (ddPCR) in EGFR mutation–positive patients with acquired EGFR-TKI resistance.
Results:
A total of 260 patients was enrolled between November 2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG 8014LTR) study. Plasma specimens from all subjects as well as tumor tissue or malignant pleural effusion or ascites from 41 patients were collected after the development of EGFR-TKI resistance. All plasma samples were genotyped successfully and the results were reported to physicians within 14 days. TKI-sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and 75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients with plasma positive for TKI-sensitizing mutations. For the 41 patients with paired samples obtained after acquisition of EGFR-TKI resistance, the concordance for mutation detection by ddPCR in plasma compared with tumor tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations and 65.9% for T790M.
Conclusion:
Noninvasive genotyping by ddPCR with cell-free DNA extracted from plasma is a promising approach to the detection of gene mutations during targeted treatment.
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OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:L.M. Montuenga, J. Heymach
- Coordinates: 12/06/2016, 11:00 - 12:30, Stolz 2
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OA11.02 - Randomized Phase 1b/3 Study of Erlotinib plus Ramucirumab in First-Line EGFR Mut + Stage IV NSCLC: Phase 1b Safety Results (ID 3827)
11:00 - 12:30 | Author(s): K. Nakagawa
- Abstract
- Presentation
Background:
Ramucirumab, an antiangiogenic IgG1 VEGFR2-targeted monoclonal antibody, and erlotinib, an EGFR tyrosine kinase inhibitor, are both active in advanced NSCLC. This global phase 1b/3 study (NCT02411448) will assess safety, tolerability and efficacy of the combination of ramucirumab with erlotinib in previously untreated patients with EGFR mutation-positive stage IV NSCLC. Here we report phase 1b safety results.
Methods:
Eligible patients with ECOG PS 0-1, an activating EGFR mutation, and previously untreated stage IV NSCLC received ramucirumab 10 mg/kg intravenously on day 1 of repeating 14-day (± 3 days) cycle and erlotinib 150 mg orally daily. Treatment continued until disease progression or unacceptable toxicity. The primary objective of part A was to assess the safety and tolerability, in terms of dose limiting toxicities (DLT), of adding the recommended dose of ramucirumab for phase 3 (part B) to standard dose erlotinib. Data were analyzed separately for Japan (JP) (cohort 1) and US/EU (cohort 2). The DLT assessment occurred during the first 2 cycles (approximately 28 days).
Results:
As of Dec 16th, 2015, 14 patients were treated in the phase 1b part of this trial and 12 were DLT evaluable (6 JP; 6 US/EU). Overall, 6 grade (Gr) 3 treatment-emergent adverse events (TEAE) were noted, with at least one TEAE in 5 patients; no serious adverse events or Gr 4-5 TEAEs occurred. In the JP cohort the median age was 73 (64-79), 57% had ECOG PS 1 and 29% had a history of smoking. Four patients (57%) experienced a Gr 3 TEAE, of which one was a DLT (elevation of alanine aminotransferase) while the others (hypertension [n=2], dermatitis acneiform, and diarrhea) were not DLTs. In the US/EU cohort the median age was 71 (31-83), 86% had ECOG PS 1, and no patients had a history of smoking. One patient experienced Gr 3 TEAE of rash; no DLTs were observed in this cohort.
Conclusion:
Enrollment on the phase 1b portion of this trial is complete and the safety results were consistent with previous combinations of antiangiogenic/erlotinib in this patient population. No unexpected toxicities were identified. Phase 3 enrollment has been initiated maintaining the dose of ramucirumab at 10 mg/kg Q2W.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-009 - Clinical Outcome of Node-Negative Oligometastatic Non-Small Cell Lung Cancer (ID 4357)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
The concept of “oligometastasis” has emerged as a basis on which to identify patients with stage IV non–small cell lung cancer (NSCLC) who might be most amenable to curative treatment. Although such patients without regional lymph node metastases tend to have a longer overall survival (OS) than those with regional lymph node involvement, limited data have been available regarding the survival of patients with node-negative oligometastatic NSCLC. We have therefore now evaluated the clinical outcome of stage IV node-negative oligometastatic NSCLC.
Methods:
Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study. Patients with regional lymph node–negative disease and a limited number of metastatic lesions (≤5) per organ site and a limited number of affected organ sites (1 or 2) were eligible.
Results:
Eighteen patients were identified for analysis during the study period. The most frequent metastatic site was the central nervous system (CNS, 72%). Most patients (83%) received systemic chemotherapy, with only three (17%) undergoing aggressive surgery, for the primary lung tumor. The CNS failure sites for patients with CNS metastases were located outside of the surgery or radiosurgery field. The median OS for all patients was 15.9 months, with that for EGFR mutation–positive patients tending to be longer than that for EGFR mutation–negative patients.
Conclusion:
Our results indicate that a cure is difficult to achieve with current treatment strategies for NSCLC patients with synchronous oligometastases, although a few long-term survivors and a smaller number of patients alive at last follow-up were present among the study cohort. There is an urgent clinical need for prospective evaluation of surgical resection as a treatment for oligometastatic NSCLC negative for driver mutations.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 3
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-002 - Phase I Study of DS-6051b, a ROS1/NTRK Inhibitor, in Japanese Subjects with Advanced Solid Tumors Harboring Either a ROS1 or NTRK Fusion Gene (ID 4366)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
Oncogenic gene fusions of ROS1 or NTRK have been reported in various cancers. DS-6051b is an orally available small molecule receptor tyrosine kinase inhibitor with high affinity for the ROS1 and NTRK receptors. Non-clinical pharmacology studies demonstrated anticancer activity of DS-6051b against several types of human tumor harboring ROS1 or NTRK fusion gene in cultured cells and xenograft models.
Methods:
This is an ongoing phase 1 study in Japanese subjects with advanced solid tumors harboring either a ROS1 or NTRK fusion gene. Subjects receive doses of DS-6051b from 400mg to 800mg once daily (QD). Pharmacokinetics (PK) samples are collected from Day1 to Day22. Primary objective is to assess the safety profile and secondary objectives are to determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D), and to assess the PK profile. The efficacy of DS-6051b is an exploratory assessment performed by investigator judgment per RECIST v.1.1.
Results:
As of June 27, 2016, a total of 9 subjects were enrolled. Median age was 51 (43-69) years, 56% were female, all 9 subjects were ROS1 fusion positive non-small cell lung cancer patients, and 3 subjects had prior crizotinib treatment. Subjects received DS-6051b at doses of 400mg QD (n=6) and 800mg QD (n=3). There were no DLTs in the 400mg QD cohort, and 2 out of 3 subjects in the 800mg QD cohort experienced DLT with grade 3 AST/ALT increased. To evaluate the MTD and RP2D more in detail, 600mg QD cohort is planned. Common adverse events were AST increased, ALT increased, diarrhea, and constipation. Among 7 patients who had target lesion, 4 subjects showed partial response, 3 subjects showed stable disease. PK data indicated the plasma drug concentration increases as the dose increases.
Conclusion:
This study is categorized as “Clinical Trial in Progress”. This study was initiated from February 2016 and estimated primary completion date will be September 2018.
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P2.06-021 - Efficacy and Safety of ASP8273 versus Erlotinib or Gefitinib as First-Line Treatment in Subjects with EGFR<Sup>Mut+</Sup> NSCLC (ID 4148)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown antitumor efficacy and prolonged progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) harboring EGFR activation mutations; however, acquired resistance often develops limiting clinical efficacy. ASP8273 is an irreversible, once-daily (QD), orally available TKI with activity against both activating and resistance EGFR mutations (ex19del, L858R, T790M). Preliminary findings from Phase 1 and Phase 2 trials in the US, Japan, Taiwan, and Korea have demonstrated antitumor activity and overall tolerability of ASP8273 at doses of 100mg–300mg.
Methods:
This global, multicenter, open-label, randomized, Phase 3 study will enroll ~600 adult subjects with Stage IIIB/IV NSCLC with EGFR-activating mutations (ex19del or L858R, with or without T790M) who have not been treated with an EGFR inhibitor TKI (NCT02588261). Subjects will be randomized 1:1 to treatment with either 300mg oral ASP8273 QD or erlotinib/gefitinib. Each site will select a comparator drug (150mg erlotinib QD or 250mg gefitinib QD) at the beginning of the study. Randomization will be stratified by ECOG status (0, 1, and 2), EGFR mutation (ex19del, L858R), comparator selected (erlotinib vs gefitinib), and race (Asian vs non-Asian). Subjects will not be enrolled if they harbor both ex19del and L858R. All subjects will begin treatment on Day 1 Cycle 1 and will continue on 28-day continuous dosing cycles until the subject discontinues (eg, due to radiologic progression as determined by RECIST or unacceptable toxicity). Dose reductions will be allowed for ASP8273 and erlotinib, but not for gefitinib. The primary study objective is PFS as assessed by independent radiological review (IRR); secondary study objectives are overall survival, best overall response rate, disease control rate and duration of response by IRR, safety/tolerability, and patient quality of life. An independent Data Monitoring Committee will oversee trial safety and the interim futility analysis. Enrollment for the trial began 26 February 2016; 46 subjects have been randomized as of 17 May 2016.
Results:
Section not applicable
Conclusion:
Section not applicable
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P2.06-037 - A Feasibility Study of Concurrent Chemoradiation Followed by Surgery for Pathologically-Proven Clinical IIIA-N2 Non-Small Cell Lung Cancer (ID 4700)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
The standard treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is definitive chemoradiotherapy. However, the strategy for resectable IIIA-N2 disease remains controversial. This phase II multi-institutional trial (WJOG5308L) was designed to evaluate the feasibility for neoadjuvant chemoradiotherapy followed by surgery (tri-modality) in patients with pathologically-proven N2 NSCLC.
Methods:
Patients with resectable IIIA-N2 (pathologically proven N2) were eligible. Neoadjuvant chemotherapy consisted of weekly paclitaxel (40mg/m2) plus carboplatin (AUC 2) for 5 weeks. Concurrent radiotherapy (RT) was prescribed with 50 Gy in 25 fractions to the mediastinum and primary tumor. Patients underwent surgical resection, unless PD disease, followed by two courses of paclitaxel plus carboplatin consolidation chemotherapy. The primary endpoint was complete resection (R0) rate. Secondary endpoints were progression-free survival, overall survival, response rate, protocol completion rate and morbidity/mortality.
Results:
From December 2011 to November 2013, 40 patients were enrolled. The median follow-up time was 33.97 (7.2-46.3) months. The radiological responses to neoadjuvant chemoradiotherapy were as follows: no complete response, 23 (57.5%) partial response, 16 (40.0%) stable disease and one (2.5%) progression. 34 of 40 patients underwent surgery. Reasons for not receiving surgery were radiation pneumonitis (n=4), PD (n=1) and delay of protocol (n=1). Of 34 resections, twenty-eight were lobectomies, three were bilobectomies, two were pneumonectomies, and one was exploratory thoracotomy. Six patients underwent sleeve lobectomy, without any complication. Thirty-two patients achieved the primary endpoint, complete resection (R0) rate 80% (32/40). Pathological complete response (PCR) rate was 30.3%. Finally, 20 patients (50%) completed all planned tri-modality treatment. The 2-year progression-free and overall survival rates for all patients were 62.5% and 75.0%, respectively. The 2-year recurrence-free survival for patients who received R0 was 61.5%. Neutropenia was the main grade 3/4 morbidity and tolerable. 30-days mortality rate was 0 %. Two treat-related deaths (late bronchial fistula) occurred. Sites of first disease recurrences were mediastinal lymphnodes (n=9, 22.5%), lung (n=8, 20%), and brain (n=4, 10%).
Conclusion:
Tri-modality treatment, neoadjuvant chemoradiotherapy followed by surgery, for resectable IIIA-N2 NSCLC seems feasible and promising.
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P2.08 - Poster Session with Presenters Present (ID 491)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Patient Support and Advocacy Groups
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.08-007 - Listen Advocate Voice - Web-Survey for the Japanese Model of Lung Cancer Advocacy by Society (ID 5651)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
In Asian countries, the concept of cancer advocacy has not been sufficiently recognized. In Japan, Lung Cancer Society (JLCS) has led the lung cancer advocacy with a part of the NPO, and adopted the 2014 Kyoto Declaration. To evaluate the awareness and attitude of lung cancer advocacy activity among patients, medical workers, and the general population in Japan, web survey was planned for the perceptions of Kyoto declaration and JLCA (Japanese alliance for lung cancer advocacy) events which were carried out by JLCS in these 2 years.
Methods:
An internet survey using survey monkey was conducted which contained 6 closed-ended (selection one or free answers) and open-ended questions, depending on the JLCA network population in June 2016.
Results:
109 people of responded involving 36% of patients and their family, 25% of MD and medical worker, 19% of pharmaceutical company officials and 16% of news media. Perception of Kyoto declaration was 21% of attendee, 27% of well-known, 13% of partial known and 39% of non-awareness. Also the number of participants to the events of JLCA is, 49% of 0 times, 17% 0f 1-2 times, 24% of 3-4 times and 11% of more than 5 times. The most sympathy events ware voted to 1) lecture by a physician 57%, 2) lecture by survivor and the participants WCLC of cancer patients 46%, 3) information in the facebook and the web site 46% 4) citizen open lecture of lung cancer 39%, 5) Performance by society ambassador 38%, 6) advocacy program in annual meetings 26% and 7) Medical seminars around the country 26%. The proportion of respondents who have a certain reputation in the activities of JLCA was 76%. The requests to JLCA is, 1) is the most participation opportunities for information of new treatment and participation opportunities to clinical trial, followed by 2) wish to participate to all the programs in the Society.
Conclusion:
In Japan, awareness about the advocacy is improved, and it was found that the expect to Society for the diverse needs through the Internet survey.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-005 - The Association between the Percentage of Anaplastic Lymphoma Kinase(ALK)-Positive Cells and Efficacy of ALK Inhibitor (ID 4621)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
The purpose of the study was to explore the association between the percentage of ALK+ cells in fluorescent in situ hybridization (FISH) and the clinical efficacy of ALK inhibitor.
Methods:
A total of 73 patients (pts) with ALK rearrangement who were identified the percentages of ALK+ cells in FISH and were treated with ALK inhibitor, were enrolled at three participating institutions. Retrospectively, we evaluated progression-free survival (PFS) by log-rank test and Kaplan–Meier method.
Results:
Median % ALK+ cells in FISH was 54% (range 15-100%). Fifty (68.5％) pts used crizotinib (CRZ) and 23 (31.5%) pts used alectinib (ALC) as the first ALK inhibitor. Among 57 pts who were evaluated by immunohistochemical (IHC) staining, 10 had no detectable expression of the ALK protein and the percentage of ALK+ cells was all within 15-29%. The PFS of pts with 15-29% ALK+ cells was shorter than that with 30% or more ALK+ cells (CRZ group: 1.4 months [95% CI: 0.2-4.2] in 15-19% ALK+ cells, 3.25 months [0.47-Not Estimated (NE)] in 20-29%, 6.77 months [4.27-12.6] in 30-100%, p < .001. ALC group: 6.4 months [3.03-16.8] in 20-29%, 23.1 months [7.8-NE] in 30-100%, p = 0.547). Moreover, among pts with 15-29% ALK+ cells, median PFS of pts with IHC- was significantly shorter than that with IHC+ (CRZ group: 1.3 vs 5.6 months, p = 0.009. ALC group: 0.87 vs 40.3 months, p = 0.004).
Conclusion:
The case in 15-29% ALK+ cells and IHC- could not obtain the benefit of the ALK inhibitor. However, if the case is IHC+, the long PFS could be expected despite the percentage of ALK+ cells in FISH.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-073 - A Phase II, Liquid Biopsy Study Using Digital PCR in EGFR Mutated, Lung Cancer Patients Treated with Afatinib (WJOG 8114LTR) (ID 4754)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
Liquid biopsy is an ideal strategy to monitor mutation status of cancer repeatedly and less invasively. In chronic myeloid leukemia, early remission of mutated cells was reported as a surrogate of longer efficacy. In epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC), to detect resistant mutation (exon20 T790M) during treatment is clinically important because newer tyrosine kinase inhibitors (TKIs) have been developed. Although some reports have mentioned the utility of liquid biopsy in EGFR mutated NSCLC, most were single-institutional, retrospective studies.
Methods:
West Japan Oncology Group (WJOG) 8114LTR is a multi-institutional, prospective liquid biopsy study in advanced NSCLC. Chemotherapy naïve, advanced NSCLC patients with EGFR-sensitizing mutation will receive afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Plasma DNA will be obtained from patients at baseline, 2, 4, 8, 12, 24, 48 weeks, and at PD. Three types of common EGFR mutations (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, pico-droplet digital PCR assay (RainDrop® system, RainDance Technologies, Billerica, MA). Primary endpoint of this study is the concordance of EGFR mutation status between tissue and plasma at baseline. Secondary endpoints are overall response rate, progression-free survival and safety. This is the first report on the primary endpoint and early remission rate based on mutated cf-DNA. This study was registered at UMIN (ID: 000015847).
Results:
Fifty-seven patients were registered and samples from 55 patients were analyzed. Clinical characteristics were as follows; median age: 69 years, male / female: 25/30, PS 0/1: 23/32, c-stage III / IV / post-operative relapse: 2/37/16, exon 19 deletion / exon 21 L858R: 28/27. Sensitivity of plasma sample was 63.6% among overall, while that was 84.6% in patients with distant metastasis. Eighty-two percent of plasma positive patients at baseline showed molecular response in plasma after two weeks of afatinib treatment. De novo T790M mutation was detected in one patient (2%) from plasma samples.
Conclusion:
Liquid biopsy seemed to be suitable especially in patients with distant metastasis. Early molecular remission (within two weeks) was observed in 70% of patients.
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P3.02b-086 - ASP8273 Tolerability and Antitumor Activity in TKI-Naïve Japanese Subjects with EGFRmut+ NSCLC: Preliminary Results (ID 4126)
14:30 - 15:45 | Author(s): K. Nakagawa
- Abstract
Background:
ASP8273, an orally administered epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits EGFR-activating mutations, has demonstrated clinical activity in ongoing Phase 1/2 studies in subjects with EGFR mutation-positive non-small cell lung cancer (NSCLC).
Methods:
EGFR TKI-naïve adult subjects (≥20 years) with EGFR mutation-positive metastatic or advanced unresectable NSCLC were enrolled in this ongoing, open-label, Phase 2 single-arm study conducted in Japan (NCT02500927). Subjects received once-daily ASP8273 300 mg until discontinuation criteria were met. The primary endpoint was tolerability; the secondary endpoint was antitumor activity (defined by RECIST v1.1).
Results:
As of 23 February 2016, 31 subjects (12M/19F; median age 64 years [range: 31–82]) with EGFR mutation-positive NSCLC have been enrolled; 25 subjects (81%) were still on study. Based on local testing, 27 (87%) of the 31 enrolled subjects had an ex19del (n=13, 42%) or a L858R (n=14, 45%) EGFR activating mutation; 4 subjects (13%) had other EGFR activating mutations, including 2 subjects (6%) with L861Q. Moreover, 3 subjects (10%) were found to have both an activating mutation as well as the T790M resistance mutation. Tolerability of ASP8273 is presented in Table 1; gastrointestinal disorders were the most commonly reported treatment-emergent adverse events (eg, diarrhea [n=24, 77%], nausea [n=12, 39%], and vomiting [n=8, 26%)]). All subjects had at least 1 post-baseline scan; 1 subject (3%) achieved a confirmed complete response, 13 subjects (42%) had a confirmed partial response, and 15 subjects (48%) had confirmed stable disease (disease control rate: 94% [n=29/31]) per investigator assessment. Figure 1
Conclusion:
These preliminary data showed that ASP8273 300 mg is generally well tolerated and demonstrates antitumor activity in TKI-naïve Japanese subjects with EGFR mutation-positive NSCLC.
