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T. Kurata
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
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OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study (ID 4799)
11:10 - 11:20 | Author(s): T. Kurata
- Abstract
- Presentation
Background:
Atezolizumab, a humanized anti-PDL1 mAb, inhibits the PD-L1/PD-1 pathway to restore tumor-specific T-cell immunity, resulting in durable anti-tumor effects. BIRCH (NCT02031458) is a single-arm Phase II study of atezolizumab monotherapy in PD-L1–selected advanced NSCLC patients, across multiple therapy lines. Primary analyses (median follow-up, 8.5 months) demonstrated a meaningful ORR with durable response in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we report updated efficacy data in 1L patients.
Methods:
1L eligibility criteria included PD-L1–selected, advanced-stage NSCLC with no CNS metastases or prior chemotherapy. PD-L1 was centrally evaluated (VENTANA SP142 IHC assay). Patients expressing PD-L1 on ≥5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3, were enrolled. Patients with EGFR mutation or ALK rearrangement must have had prior TKI treatment. Atezolizumab 1200mg was administered IV q3w until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility(IRF)-assessed ORR. Secondary endpoints included investigator(INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.
Results:
With a median follow-up of 14.6 months, median OS was not reached in TC3 or IC3 patients and was 20.1 months in TC2/3 or IC2/3 (ITT) patients; INV-assessed ORR was 32% and 24%, respectively (Table). Furthermore, ORR was 31% for mutant EGFR (n=13) vs 20% for wild-type EGFR patients (n=104), and 27% for mutant KRAS (n=33) vs 21% for wild-type KRAS patients (n=67). No new safety signals were observed. Updated efficacy (including IRF ORR), safety and exploratory biomarker analyses will be presented.
Conclusion:
With longer follow-up, atezolizumab continued to demonstrate promising efficacy in 1L NSCLC. These results indicate that atezolizumab has durable efficacy in the 1L setting, in EGFR and KRAS mutant and wild-type tumors, and support ongoing Phase III trials evaluating atezolizumab vs chemotherapy in 1L NSCLC.
NE, not estimable.[a ]TC ≥50% or IC ≥10% PD-L1–expressing cells.[b ]TC or IC ≥5% PD-L1–expressing cells.Endpoint(95% CI) TC3 or IC3[a](n=65) TC2/3 or IC2/3[b](n=139) INV ORR, % 32% (21.2–45.1) 24% (16.9–31.7) EGFR mutant/wild-type, % 25%/29% 31%/20% KRAS mutant/wild-type, % 38%/27% 27%/21% mDOR, mo 13.1 (8.5–NE) 13.1 (9.9–17.5) mOS, mo NE (12.0–NE) 20.1 (20.1–NE) 12-mo OS rate, % 61% (48.8–73.8) 66% (57.9–74.5) mPFS, mo 7.3 (4.9–12.0) 7.3 (5.6–9.1) 12-mo PFS rate, % 36% (23.8–48.8) 32% (24.0–40.7)
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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: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-023 - A Phase III Study Comparing Gefitinib and Inserted Cisplatin plus Pemetrexed with Gefitinib for EGFR-Mutated Advanced Non-Squamous NSCLC (ID 4587)
14:30 - 14:30 | Author(s): T. Kurata
- Abstract
Background:
Overcoming and prevention of acquired resistance to EGFR-TKIs in the treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC) is a critical issue. Although third-generation EGFR-TKIs, such as osimertinib, which are potent against EGFR carrying the T790M mutation, have been developed, they are insufficient to overcome other resistance mechanisms. We hypothesized that the insertion of platinum-doublet chemotherapy with EGFR-TKIs might prevent the emergence of acquired resistance to EGFR-TKIs and prolong the patient survival. An early phase II study of inserted cisplatin and docetaxel with gefitinib showed promising outcomes, including a median progression-free survival of 19.5 months and median survival time of 48.0 months.
Methods:
Figure 1 This study (JCOG1404 / WJOG8214L: AGAIN study) is an intergroup, multicenter, randomized phase III study conducted by the Japan Clinical Oncology Group (JCOG) and the West Japan Oncology Group (WJOG). The objective of this study is to confirm the superiority, in terms of the overall survival, of the study treatment, described below, over gefitinib monotherapy. As the study treatment, gefitinib are administered on days 1-56. Then, after a two-week drug-free period, three cycles of cisplatin and pemetrexed are administered on days 71, 92, and 113. Thereafter, gefitinib is re-started on day 134 and continued until disease progression. The secondary endpoints are progression-free survival, response rate, adverse events, severe adverse events and proportion of EGFR T790M mutation positive in the tumor samples at disease progression. The key eligibility criteria are: patients with advanced or recurrent non-squamous NSCLC harboring EGFR activating mutations (exon 19 deletion or exon21 L858R), age 20 to 74 years, and PS 0 or 1. This study was started in December 2015, and a total of 500 patients will be enrolled over a period of 3 years. This trial has been registered at UMIN-CTR[umin.ac.jp/ctr/] as UMIN000020242.
Results:
Section not applicable
Conclusion:
Section not applicable
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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-050 - A Phase I/II Study of Erlotinib, Carboplatin, Pemetrexed and Bevacizumab for Advanced Non-Squamous NSCLC Harboring EGFR Mutation (ID 6333)
14:30 - 14:30 | Author(s): T. Kurata
- Abstract
Background:
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) drastically prolonged progression free survival (PFS) of patients with non-squamous non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, most cases show tumor regrowth after approximately only ten months treatment, and the prognosis is still poor. Then it is necessary to make new strategy of treatment for NSCLC harboring EGFR mutation, and we designed phase I/II study of Erlotinib, Carboplatin, Pemetrexed and Bevacizumab in chemotherapy-naïve patients with EGFR mutation positive advanced non-squamous NSCLC.
Methods:
In the phase I part, eligible patients were administrated orally Erlotinib daily, and Pemetrexed, Carboplatin and Bevacizumab intravenously every three weeks for four cycles with maintenance of Pemetrexed and Bevacizumab until PD. The dose level of Erlotinib were 100mg in level 1 and 150mg in level 2. And the dose of pemetrexed, carboplatin and bevacizmab were fixed as 500mg per m[2], AUC6 and 15mg per kg. The dose limiting toxicities are Grade (Gr) 3-4 neutropenia with fever or infection, Gr 4 leukopenia lasting for 7 days or longer, Gr 4 thrombocytopenia, Gr 3-4 uncontrollable non-hematological toxicity and delayed administration of the subsequent course by more than 2 weeks due to adverse events.
Results:
Six patients were enrolled in Phase I part (level 1-three, level 2-three). The median age was 71.5 y.o. (Range, 46-76 y.o). Male was one and female were five. Histology of all patients was adenocarcinoma, and Ex19del was four and Ex21 L858R was two. A Gr3 of neutropenia without fever was observed in level 1, and a Gr3 of neutropenia without fever, three Gr3 thrombocytopenia and a stomatitis were observed in level 2(Table1). No DLT events were observed in Phase I. Table1Grade 1 2 3 ANC 1 1 PLT 2 Anemia 2 Stomatitis 1 1 Nausea 1 2 Appetite loss 1 2 Rash 1 Transaminase 1 T.Bil 1 Fatigue 1 Bleeding 1 Diarrhea 1
Conclusion:
The recommend dose of Erlotinb is 150mg daily.
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P3.02b-097 - Experience of Re-Biopsy (Biopsy at Progression) of EGFR Mutant Non-Small Cell Lung Cancer Patients in Japan: A Retrospective Study (ID 4049)
14:30 - 14:30 | Author(s): T. Kurata
- Abstract
Background:
To confirm mechanisms of resistance to targeted therapy and to evaluate future treatment strategy, biopsy at progression is important and necessary. Since biopsy at progression is not standard of care, we investigated real-world clinical practice in Japanese patients with non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) gene mutation.
Methods:
This was a retrospective, multi-center, observational study in Japan. EGFR mutation positive NSCLC patients who developed disease progression after treatment by EGFR tyrosine kinase inhibitor were enrolled. The primary objective was the success rate of re-biopsy (biopsy at progression). The secondary objectives were differences of between the first biopsy and re-biopsy (e.g. sampling method, target organ of biopsy) and complications associated with re-biopsy.
Results:
395 patients were evaluated, median age was 63 years, and the most common histological type was adenocarcinoma (96.2%). Success rate of re-biopsy was 79.5% (314/395) of patients. Compared with the first biopsy, surgical biopsy increased from 1.8% to 7.8%, percutaneous tissue biopsy increased from 7.6% to 29.1%. Most commonly performed gene mutation tests using specimen collected by re-biopsy were EGFR (94.3%), EML4-ALK (22.0%) and KRAS (14.3%). T790M mutation was detected in 147 (49.7 %) out of 296 patients. 23 patients (5.8%) had complications associated with re-biopsy, the most common complication was pneumothorax. A repeated re-biopsy was successful in 87.5% (28/32) of patients.Table. Re-biopsy success rate by site and sampling method No. of patients Success rate (%) By Site Primary site 220 168 (76.4%) Metastatic site 121 103 (85.1%) Lymphnodes 50 40 (80.0%) Others 4 3(75.0%) By sampling method Transbronchial biopsy; forceps 204 147(72.1%) Transbronchial biopsy; needle 41 34 (82.9%) Percutaneous needle biopsy under CT guidance 77 66 (85.7%) Percutaneous needle biopsy under ultrasonic guidance 36 34 (94.4%)
Conclusion:
The observed success rate of re-biopsy was approximately 80% in this study. T790M detection rate was comparable to the previously reported studies. Re-biopsy for the EGFR TKI failure NSCLC patients is feasible in Japan.
