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P.K. Cheema
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-029 - CheckMate 169: Safety/Efficacy of Nivolumab in Canadian Pretreated Advanced NSCLC (including Elderly and PS 2) Patients (ID 9042)
09:30 - 09:30 | Author(s): P.K. Cheema
- Abstract
Background:
Nivolumab demonstrated efficacy and safety in patients with previously treated advanced/metastatic NSCLC in the two phase 3 trials CheckMate 017 and 057 (median OS, 9.2–12.2 months; 1-year OS rate, 42–51%; 2-year OS rate, 23–29%; any-grade treatment-related AEs [TRAEs], 68%; grade 3–4 TRAEs, 10%). As patients with ECOG PS 2 were excluded from these phase 3 trials, there is limited evidence for nivolumab efficacy in this patient subgroup. CheckMate 169 (NCT02475382) is an expanded access program (EAP) of nivolumab in patients with advanced NSCLC and disease progression after ≥1 prior systemic therapy; efficacy/safety results from the Canadian cohort are presented here.
Method:
Eligible patients were aged ≥18 years with relapsed stage IIIb/IV NSCLC and an ECOG PS of 0–2 who had received ≥1 prior platinum-containing therapy. Patients with carcinomatous meningitis or untreated brain metastases were excluded. Nivolumab (3 mg/kg IV Q2W) was administered until disease progression or unacceptable toxicity for a maximum of 2 years. In addition to providing nivolumab to patients, the primary objective was to assess safety and OS. Outcomes in specific patient subgroups, including elderly patients (aged ≥70 years) and those with poor performance status (PS 2), were assessed in post hoc analyses.
Result:
Of 161 patients treated in Canada, 53% were male, 94% were current/former smokers, 32% had squamous NSCLC, and 43% had received ≥2 prior therapies. 30% were aged ≥70 years and 19% had an ECOG PS of 2. At the time of analysis, 76% of patients had discontinued treatment. Nivolumab was well tolerated. In the overall population, TRAEs of any grade were reported in 69% of patients, with grade 3 or 4 events in 14%; no TR deaths occurred. 9% of patients discontinued due to TRAEs. The safety profile of nivolumab in patient subgroups (age ≥70 years and PS 2) was similar to the overall population. The median OS (95% CI) in the overall population was 9.1 months (7.5, 14.4), with a 1-year OS rate of 44%. The median OS was 8.0 months (5.3, 12.9) for elderly patients and 5.9 months (3.6, 7.9) for those with PS 2. The presentation will include patient case studies from the subgroups.
Conclusion:
In this EAP of nivolumab in Canadian patients with previously treated NSCLC, safety and OS were consistent with observations from prior controlled trials. Safety in elderly patients and those with PS 2 was consistent with the overall population.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-005 - ASTRIS: A Real World Study of Osimertinib Treatment in Patients with EGFR T790M Positive Advanced NSCLC; Interim Analysis (ID 7884)
09:30 - 09:30 | Author(s): P.K. Cheema
- Abstract
Background:
Osimertinib is a third-generation, CNS active EGFR-TKI that potently and selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations in non-small cell lung cancer (NSCLC). We report interim clinical and molecular diagnostic testing results from a predefined interim analysis of the ongoing ASTRIS study (NCT02474355).
Method:
Patients (pts) received osimertinib 80 mg once daily. Eligible pts had advanced NSCLC that had progressed on prior EGFR-TKI therapy and with a T790M mutation determined by local validated molecular test, WHO performance status (PS) 0−2, acceptable organ and bone marrow function and no history of interstitial lung disease or QTc prolongation. Asymptomatic, stable CNS metastases were permitted. The primary efficacy outcome was overall survival; other outcomes included local test methods, specimen type, EGFR mutations identified, investigator-assessed response rate (RR), progression-free survival and time to treatment discontinuation. Safety data are also reported.
Result:
From 18 Sept 2015 to the planned 3 Nov 2016 data cut-off (DCO), 1217 pts received osimertinib 80 mg once-daily across 14 countries with a median age 64 yrs (27–92 yrs), 67% female, 61% White, 37% Asian, 87% WHO PS 0/1, 44% prior chemotherapy, 45% prior radiotherapy. All pts tested positive for T790M; T790M was reported alone in 185 pts (15%). The most common testing methods were PNA-Clamp 317 pts (27%), Qiagen therascreen 254 pts (22%), and Roche cobas 204 pts (17%). Exon 19 deletion was the most common co-occurring mutation with T790M (57%), followed by L858R (27%). Tissue or cytology specimens were used in 720 pts (59%), plasma in 433 pts (36%), and other specimens in 64 pts (5%). At DCO, the median duration of exposure was 3.8 months (<1–13.2 months) with a median follow-up time of 4.1 months (<1−14 months). In pts evaluable for response, the investigator-assessed RR was 64% (569/886; 95% CI 61, 67). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 122 pts (10%) and 54 pts (4%), respectively. Serious AEs were reported in 165 pts (14%) and AEs leading to death in 28 pts (2%).
Conclusion:
ASTRIS is the largest reported global study of osimertinib in pts with T790M-positive NSCLC identified by a wide array of molecular testing methods and from various specimen types. Considering this breadth of T790M testing, the clinical activity of osimertinib is like that observed in the clinical trial program and no new safety signals were identified.
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P3.01-019 - Canadian Multicentre Validation Study of Plasma Circulating Tumour DNA for Epidermal Growth Factor (EGFR) T790M Testing (ID 8878)
09:30 - 09:30 | Author(s): P.K. Cheema
- Abstract
Background:
Plasma detection of EGFR T790M mutations in circulating tumour DNA (ctDNA) of advanced lung cancer patients with acquired resistance to EGFR tyrosine kinase inhibitor (TKI) has been proposed as alternative to tumor re-biopsy. This national validation study across Canadian centres aimed to establish the sensitivity and specificity of plasma detection of T790M as a clinical test using digital droplet (dd)PCR and next generation sequencing (NGS) assays.
Method:
Canadian patients at 7 centres undergoing screening for ASTRIS (NCT02474355) were invited to participate in this companion blood-based study. Patients with acquired resistance to EGFR TKI consented to collection of blood samples and demographic data. Samples were analysed using ddPCR and/or NGS platforms available at 4 molecular diagnostic laboratories across Canada. Concordance between the results of plasma T790M assayed in these 4 laboratories with reference tissue/plasma testing conducted for ASTRIS was assessed.
Result:
63 patients participated; the median age was 64 years (range 31-87), 69%(40/58) were Asian; 55%(33/60) were male. All patients received prior EGFR TKI, 17%(10/60) also received prior chemotherapy. Reference testing for EGFR T790M for ASTRIS eligibility identified positive T790M(+) results for 31(49%), negative(-) for 30(48%) and indeterminate(i) results for 2(3%) patients. One laboratory tested all 63 patient samples using both ddPCR and NGS (Oncomine Lung cfDNA assay), another laboratory tested 18 samples using ddPCR and NextSeq, a third tested 10 samples using ddPCR and COBAS EGFRv2, and a fourth tested 6 samples using Ion Torrent PGM. A total of 188 tests were performed including 91 by ddPCR, 87 NGS and 10 COBAS assays. Combining test results for each patient, 60%(38/63) of patient plasma samples were T790M+, 23(37%) were T790M-, and 2(3%) were inconclusive. Of 31 patients with reference T790M+ results from ASTRIS, 23(74%) had T790M detected in plasma, 6(19%) did not (T790M-), and 2(7%) had indeterminate (T790Mi) plasma results. For 30 patients with T790M- reference results from ASTRIS, 13(43%) had plasma T790M+ and 17 plasma T790M- results. The 2 patients with T790Mi by reference testing both had T790M+ results from plasma. Altogether, 47%(15/32) of patients deemed to have T790M-/i tumours by reference testing were found to have T790M+ results by plasma in this multicentre study. Combining results from both tissue and plasma testing, 73%(46/63) of study patients had T790M+ results.
Conclusion:
Plasma ctDNA testing in this multicentre Canadian study identified a significant number of additional patients eligible for osimertinib therapy beyond routine biopsy tissue testing for EGFR T790M.
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P3.01-062 - The Perceived Value of Avoiding Biopsy: Patients' Willingness to Pay for Circulating Tumour DNA T790M Testing (ID 10004)
09:30 - 09:30 | Author(s): P.K. Cheema
- Abstract
Background:
Plasma detection of circulating tumour DNA (ctDNA) with T790M mutation in the context of EGFR tyrosine kinase resistance has been shown to have high concordance with tissue biopsy specimens. In a public healthcare system, patients’ perceived value of a test and willingness to pay can inform policy decisions regarding implementation and funding of a novel technology.
Method:
As part of screening for the ASTRIS clinical trial (NCT02474355), Canadian patients were invited to participate in a national validation study of blood-based ctDNA T790M testing. Eligible patients had acquired resistance to EGFR TKI and consented to collection of blood samples, demographic data, and completion of a structured interview measuring their perceived value of blood-based ctDNA testing as an alternative to tumour biopsy. They were asked about their willingness to pay for testing using both open-ended and iterative bidding approaches. The study was supported by a grant from AstraZeneca.
Result:
60 patients were accrued to the study. Median age of the cohort is 64 years (range 31-87); 69% are Asian (40/58); 55% (33/60) are male. All patients had received prior EGFR kinase inhibitor treatment, with 67% (45/60) receiving gefitinib. 17% of patients also received chemotherapy (10/60). A median of 1 prior line of therapy had been received (range 1-6). All patients preferred to have the blood test over repeat tumour biopsy. Patients estimated a mean reasonable price to pay for the test of $954; median $300 (range 0-10,000; IQR 150-800). Patients were personally willing to pay a mean of $281; median $100 (range 0-2500; IQR 33-350).
Conclusion:
In a public health system that covers the cost of standard diagnostic tests, Canadian patients indicated a willingness to pay out of pocket for peripheral blood detection of ctT790M. Patients have high perceived value of ctDNA and prefer it to tumor biopsy.
