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Raffaele Califano
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-26 - Single-Centre Experience of Clinical Outcomes for Advanced Lung Cancer Patients in Phase I Clinical Trials. (ID 13932)
16:45 - 18:00 | Author(s): Raffaele Califano
- Abstract
Background
Response rates for patients enrolled in early phase clinical trials have historically been reported as 5-10%. An unprecedented number of novel therapeutic options and emerging therapies in lung cancer (LC) have resulted in greater emphasis on early phase clinical trials and molecular stratification.
We aimed to evaluate outcomes for patients with LC treated since 2015 with novel agents or combination strategies within an expanding early phase clinical trials unit at The Christie Hospital, Manchester, UK.
a9ded1e5ce5d75814730bb4caaf49419 Method
A database of patients consented to phase I clinical trials was interrogated for LC patients recruited over a three-year period. Clinical characteristics including histological sub-type, line of therapy, molecular phenotype, smoking status and ECOG performance status (PS) were collected for each patient. Patient records were reviewed for clinical trial allocation, treatment response, progression-free survival (PFS), and overall survival (OS).
4c3880bb027f159e801041b1021e88e8 Result
Over a three-year period to March 2018, 153 lung cancer patients were consented to Phase I clinical trials of Investigational Medicinal Products, of whom 113 (74%) commenced treatment. The median age of patients treated was 64y (range 28-84) with a male predominance (54%). All patients had a PS of 0-1 and 25% were non-smokers. Histological subtypes included non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and mesothelioma. The overall response rate (RR) by RECIST criteria was 27% across all patients, with a disease control rate of 73%. Median PFS was 6 months, and median OS was 11 months in the entire cohort. Compared with patients with NSCLC, patients with SCLC had worse PFS (7mo vs 3mo, p=0.001) and RR (35% vs 0%). The 28 trials recruiting LC patients in the unit during this period involved therapies targeting EGFR and ROS1, PI3K-mTOR-AKT and RAS-RAF-MEK signalling, DNA repair genes, cell-surface protein overexpression and genes implicated in immune signalling. Novel agents included small molecule inhibitors, monoclonal antibodies, and antibody-drug conjugates, in addition to targeted agents combined with chemotherapy or immune checkpoint inhibitor combinations. Patients had between 0-5 prior lines of therapy with no difference in PFS, OS or RR regardless of prior treatment lines.
8eea62084ca7e541d918e823422bd82e Conclusion
Our data demonstrate clear benefit for lung cancer patient participation in early phase clinical trials. Novel therapeutic agents and evolution of early phase clinical trial design have resulted in promising options for patients with NSCLC, with RR>30% within our unit, regardless of prior treatment status. However, outcomes for SCLC patients lag behind and new therapeutic options are urgently needed.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-01 - Brigatinib Use in England – Where Next? (ID 14260)
16:45 - 18:00 | Author(s): Raffaele Califano
- Abstract
Background
ALK positive NSCLC is estimated to account for 1,600 cases per year in England. Brigatinib is a next generation ALK inhibitor with proven efficacy after crizotinib but its role in 1st line is still under investigation. If licensed in Europe it may further extend survival for this rare group of patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a multicentre retrospective study across hospitals from the National Health System (NHS) in England on ALK positive patients who were offered treatment with the newer generations of ALK inhibitors. For this analysis, patients who received treatment with brigatinib through Compassionate use program or clinical trials between 2012 and 2018 were selected. The primary aims were time of exposure to brigatinib (as a surrogate of clinical benefit) and the objective response rate (ORR). The secondary aim was the incidence of grade 3-4 toxicity. And an exploratory aim analysed the value of ALK inhibitors treatment sequence.
4c3880bb027f159e801041b1021e88e8 Result
A total of 30 patients with an ALK positive lung adenocarcinoma were included with a median age of 50 years. 53% of patients were female and 77% never smoked. 90% presented at diagnosis with metastatic disease and 63% developed brain metastasis. The median follow-up time since the start of brigatinib was 9.7 months and 53% of patients were on brigatinib at the time of analysis. In 57% of cases brigatinib was only used after a 2nd line of treatment. Only 6 patients were treated in the first line setting. The overall median time of exposure was 12.1 months (95% CI, 4.7 to 19.6) with a maximum exposure of 30 months. The ORR was 50% within the 28 evaluable patients. Median overall survival was not reached. Only 1 patient had grade 3-4 toxicity with increased AST. The use of brigatinib in 1st and 2nd lines (13 patients) did not reach a median exposure time and the ORR was 69%. Brigatinib post-crizotinib (9 patients) had a higher exposure time compared with post-ceritinib (13 patients), respectively, 9.1 (95% CI, 0.5 to 25.7) and 6.6 months (95% CI, 2.6 to 10.6). However the first sequence was more often used in 1st/2nd lines (50% vs 15%).
8eea62084ca7e541d918e823422bd82e Conclusion
Brigatinib is an active and very well tolerated drug. Despite being used mainly in heavily pre-treated patients, our data confirm a meaningful clinical benefit in this population. Its efficacy may be higher in earlier lines and we found no clear signal favouring a specific sequence of treatment.
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PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
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PL02.03 - Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (ID 11155)
08:30 - 08:40 | Author(s): Raffaele Califano
- Abstract
- Presentation
Background
Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).
This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).
275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.
Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.
BIRC-Assessed Endpoint, % Brigatinib
(n=137)
Crizotinib
(n=138)
P-Value All patients ORRa 76 (68–83b) 73 (65–80b) Confirmed ORR 71 (62–78b) 60 (51–68b) 0.0678 With any intracranial CNS metastases (n=43) (n=47) iORRa 79 (64–90b) 23 (12–38b) Confirmed iORR 67 (51–81b) 17 (8–31b) <0.0001 Median iPFS, months NR (11–NRb) 6 (4–9b) 1-year iPFS 67 (47–80b) 21 (6–42b) HR 0.27 (0.13–0.54) <0.0001c With measurable intracranial CNS metastases (n=18) (n=21) iORRa 83 (59–96b) 33 (15–57b) Confirmed iORR 78 (52–94b) 29 (11–52b) 0.0028 aResponse, ≥1 assessment; b95% CI; cLog-rank.
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