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F.Y. Wu
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MA04 - HER2, P53, KRAS and Other Targets in Advanced NSCLC (ID 380)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
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MA04.03 - Preliminary Results of a Phase II Study about the Efficacy and Safety of Pyrotinib in Patients with HER2 Mutant Advanced NSCLC (ID 6069)
16:12 - 16:18 | Author(s): F.Y. Wu
- Abstract
- Presentation
Background:
There is still an unmet need for targeted drugs in non small cell lung cancer (NSCLC) patients with HER2 mutation. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This phase II trial is designed to evaluate the safety and efficacy of pyrotinib in patients with HER2 mutant advanced NSCLC.
Methods:
A single arm prospective phase II trial was undergone to evaluate the efficacy and safety of Pyrotinib in patients with HER2 mutant advanced NSCLC in a single center of Shanghai Pulmonary Hospital, Tongji University(NCT 02535507). Pyrotinib was administrated 320mg or 400mg orally once a day. Next generation sequencing or ARMS was used to identify the patients with HER2 mutation. The primary endpoint was objective response rate and the secondary endpoints were side effect, progression free survival and overall survival.
Results:
From Jul 15 2015 to Jul 21, 2016, 11 patients with her2 mutated advanced NSCLC were enrolled into this study. Among them, the median age was 58 years old, 6 were male, 4 were smoker, ECOG PS 0/1/2 were 5/6 and all of them were adenocarcinoma. None of them received pyrotinib as the first line therapy and the median previous anti-cancer regimen was 2. 9 patients had the details variants of HER2 mutation including 7 with exon 20 776YVMA, 1 with exon 20 770AYVM and 1 with 2326G>ATTT. All of them evaluated the response, including 54.5% with partial response(6/11), 27.3% with stable disease(3/11) and 18.2% with progressive disease(2/11). 1 patient got response to pyrotinib after progressed from afatinib. 5 patients were still on the study and the median PFS was 6.2 months. Side effects were mild including 4 with grade I/II diarrhea, 2 with grade II fatigue, 2 with grade I rash and 1 with dispnea.
Conclusion:
Pyrotinib showed promising results about the ORR and PFS together with mild toxicity in patients with HER2 mutant advanced NSCLC, further multicenter large scale phase II study is initiated to validate the results in this study.
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MA15 - Immunotherapy Prediction (ID 400)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:O. Arrieta
- Coordinates: 12/07/2016, 14:20 - 15:50, Schubert 1
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MA15.03 - The Predictive Value of Mutation/Neoantigen Burden from ctDNA on the Efficacy of PD-1 Blockade in Advanced NSCLC (ID 5884)
14:32 - 14:38 | Author(s): F.Y. Wu
- Abstract
Background:
Immune checkpoint, PD-1, inhibitors, have been approved to treat advanced NSCLC patients without oncogenic driver in the second-line setting based on durable clinical benefit. It has been demonstrated that the overall mutational burden in tumor tissue was significantly associated with progression free survival (PFS) of advanced NSCLC patients treated with PD-1 inhibitor. However, tumor tissue may not be available from all patients at any time during PD-1 blockade therapy. Therefore, the purpose of this study was to explore the predictive value of mutation/neoantigen burden from ctDNA on efficacy of PD-1 inhibitors.
Methods:
We treated advanced NSCLC patients without oncogenic drivers with PD-1 inhibitor in the second or more line setting. The whole-exome of tumor tissues and ctDNA at baseline and ctDNA at every time of efficacy evaluation from these patients were sequenced by NGS. The hybrid-capture-enriched libraries were sequenced on the Illumina HiSeq 4000 platform with 75-base paired-end reads, sequencing depth was 300 for ctDNA whole-exome sequencing. We compared the results of whole-exome sequencing between patients who achieved objective response to PD-1 inhibitor and patients who experienced disease progression. Besides, we also compared the results of whole-exome sequencing between baseline ctDNA and ctDNA extracted at efficacy evaluation.
Results:
Up to now, a total of 23 patients treated with PD-1 inhibitor received efficacy evaluation at least once in this study. Of them, 4 patients achieved partial response (PR), 3 patients achieved stable disease (SD). Of 4 patients with PR, 3 patients were found to harbor high mutation burden (more than 400 nonsynonymous mutations) from ctDNA and only 1 patient harbored mutation burden of less than 100 from ctDNA at baseline. We found the mutation or neoantigen burden from ctDNA changed during PD-1 blockade therapy. The efficacy of PD-1 inhibitor appeared to be more significantly associated with neoantigen burden rather than mutation burden. Only one ctDNA sample was found positive for MSH6 mutation (C1337X) and all baseline ctDNA samples were negative for microsatellite instability (MSI) status.
Conclusion:
Evaluating nonsynonymous mutation burden/neoantigen burden from ctDNA was feasible in advanced NSCLC patients treated with PD-1 inhibitors. The predictive value of neoantigen burden from ctDNA on the efficacy of PD-1 inhibitor may be better than that of mutation burden in advanced NSCLC. It may not be feasible to determine the status of mismatch-repair deficiency and MSI using ctDNA samples in advanced NSCLC. An expanded study is ongoing. More details will be presented in the conference.
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P3.02c - Poster Session with Presenters Present (ID 472)
- 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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P3.02c-025 - Safety and Efficacy of Apatinib in Patients with Previously Heavily Treated Advanced Non-Squamous Non-Small-Cell Lung Cancer (ID 4559)
14:30 - 14:30 | Author(s): F.Y. Wu
- Abstract
Background:
Apatinib is a tyrosine kinase inhibitor which selectively inhibits VEGFR-2 and also represents mild inhibition to PDGFR, c-Kit and c-src. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis and tumor cell proliferation. Previous clinical trials have demonstrated its obvious antitumor activity in various cancer type. Thus we designed this phase II, open-label, single-armed, prospective study (NCT02515435) to investigate the efficacy and safety of apatinib for heavily treated, advanced non-squamous NSCLC patients who are not applicable to current standardized therapy or other clinical trials.
Methods:
We prospectively enrolled 40 patients with previously heavily treated advanced non-squamous NSCLC. All patients received apatinib with a dose of 500mg, q.d., p.o. Efficiency was evaluated initially 4 weeks later and then every 8 weeks until disease progression, death, or unacceptable toxicity. The primary end point of this study was overall response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS).
Results:
Forty patients were enrolled in the study with a median age of 61. 15% of patients received apatinib as second-line therapy, 40% of patients received apatinib as third-line therapy, and 60% as forth-line to twelfth-line therapy. Nine patients were found with activated EGFR mutation. Among all the enrolled patients, 38 patients had clinical evaluation and the other 2 received treatment of apatinib less than one month. Within 33 patients who had available image efficiency, 6 were identified as PR,17 SD and 10 PD, no CR was observed. The ORR was 18.18 %, the DCR was 69.69 %. The ORR for patients with EGFR mutation positive and negative were 25% and 16% separately. The median PFS was 3.22 months (95% CI, 2.20-4.17 months). Among them, 6 patients received the treatment of apatinib more than five months. The 6-month OS rate was 76.98% (95% CI, 61.68%-92.27%), the 12-month OS rate was 57.48% (95% CI, 28.75%-86.20%). Common treatment-related adverse events were proteinuria (25%), hypertension (17.5%), and hand-foot-skin reaction (HFSR)(27.5%). Severe adverse events included grade 3 hypertension (5%), HFSR (5%), and thrombocytopenia (5%), no grade 4 or 5 adverse events were observed. No un-expected adverse events were found.
Conclusion:
Apatinib as a monotherapy had a promising overall response together with an acceptable side effect in patients with previously heavily treated advanced non-squamous NSCLC. A phase III study comparing apatinib monotherapy with placebo as 3rd/4th setting in advanced non-squamous NSCLC is ongoing to further evaluated the efficacy of apatinib (NCT02332512).
