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C. Mulatero
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-015 - STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC (ID 4269)
14:30 - 14:30 | Author(s): C. Mulatero
- Abstract
Background:
STOMP (ISRCTN 73164486, CRUK/10/037, EudraCT 2010-021165-76) is a randomised, double-blind, placebo-controlled phase II trial to evaluate activity and safety of the PARP inhibitor olaparib (AstraZeneca) as maintenance treatment for patients with chemo-responsive small cell lung cancer (SCLC). Two schedules of olaparib oral tablets were investigated: 300mg twice daily (bd) or 200mg three times daily (tds).
Methods:
Eligible patients had pathologically confirmed SCLC with response to first line chemotherapy or chemo-radiotherapy. Patients were stratified by metastasis-status and prior radiotherapy and randomised in a 2:2:1:1 ratio to: olaparib tds, olaparib bd, placebo tds or placebo bd. Placebo arms were pooled for analyses. Primary outcome was progression-free survival (PFS). There is 80% power to detect a difference of 3 months in PFS (from 4.8 months) between treatments based on a one-sided 5% significance level. Key secondary outcome measures were overall survival (OS), adverse events (AEs) and quality of life.
Results:
Between November 2013 and December 2015, 220 UK patients were randomised. Arms were well balanced for stratification factors of prior radiotherapy (89% Yes) and metastasis status (66% M1) as well as sex (46% M) and age (median=64, range 42-89). Median follow-up for 31 event-free patients was 14 months (range 0–24). Median PFS was 2.6 (90%CI 1.8, 3.7), 3.6 (90%CI 3.1, 6.0) and 3.6 (90%CI 3.1, 4.7) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in PFS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.87; 90% CI 0.64, 1.18; stratified logrank p=0.29) or the tds arm (0.89; 90% CI 0.67, 1.20; p=0.43). Median OS was 8.9 (90%CI 7.0, 11.9), 9.9 (90%CI 7.6, 12.9) and 9.0 (90%CI 6.6, 11.8) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in OS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.97; 90% CI 0.69, 1.37; stratified logrank p=0.73) or the tds arm (1.05; 90% CI 0.76, 1.46; p=0.73). The most common AEs on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. 68 patients discontinued treatment citing AEs (17 placebo, 26 olaparib bd, 25 olaparib tds).
Conclusion:
There is no evidence that either the bd or tds regimen for olaparib improves PFS or OS in an unselected population. The AE profile for olaparib in SCLC is similar to that observed in other studies.
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P3.02b - Poster Session with Presenters Present (ID 494)
- 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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P3.02b-046 - Afatinib Benefits Patients with Confirmed/Suspected EGFR Mutant NSCLC, Unsuitable for Chemotherapy (TIMELY Phase II Trial) (ID 4195)
14:30 - 14:30 | Author(s): C. Mulatero
- Abstract
Background:
Afatinib is licensed for EGFR-mutant NSCLC without prior TKI therapy, but its efficacy and toxicity in patients unsuitable for platinum-doublet chemotherapy is unknown. One previous study suggested that TKIs could benefit medically unfit EGFR-mutant East Asian patients. We conducted the first such study in a Western population.
Methods:
Single arm phase-II trial. Eligible patients with histologically confirmed NSCLC, comorbidities precluding chemotherapy, with either: (i) confirmed EGFR-mutation and PS 0-3, or (ii) suspected EGFR-mutation (no suitable tissue for genotyping or failed genotyping), but never/former-light smoker, adenocarcinoma and PS 0-2. Patients received oral afatinib (20-40mg daily) until disease progression/toxicity. CT scans performed 4 weeks after starting treatment then every 8 weeks in first year until progression, thereafter every 12 weeks. Primary endpoint was 6-month RECIST-defined progression-free-survival (target 30%).
Results:
39 patients were recruited across 14 UK centres (March 2013-August 2015). Median age 72 years (range 36-90); 30 females, 9 males; 20 confirmed and 19 suspected EGFR-mutant; 8 former and 11 never smokers (among suspected EGFR-positives); 1,1,7,30 in each stage IA,IIIA,IIIB,IV; and 27 PS 0-1, 12 PS 2-3. As of July 2016, 7 patients were still taking afatinib (median time on drug 11 months, range 10-16), and 11 stopped for toxicity. 23/39 patients had at least one grade ≥3 afatinib-related toxicity (all gd3, except two with gd4 [sepsis and hypokalemia], one fatal pneumonitis), mainly: n=13 diarrhoea; n=4 vomiting; n=3 dehydration; n=3 mouth ulcer, all expected for afatinib, and unsurprising in this unfit group. The table shows efficacy. 6-month PFS rate (58%) far exceeded the 30% target; similarly for patients with confirmed (74%) or suspected (41%) EGFR-mutation.Efficacy (26 PFS events, 21 deaths)
Rate (95%CI) at month Alive & progression-free Overall-survival All patients (n=39) 6 58% (43-74) 74% (60-88) 12 34% (18-50) 64% (48-80) Median, months (95%CI) 7.9 (4.6-10.2) 15.5 (10.9-25.1) Confirmed EGFR mutant (n=20) 6 74% (55-94) 85% (69-100) 12 47% (24-70) 85% (69-100) Median, months 10.2 (5.9-not estimable) Not reached Suspected EGFR mutant (n=19) 6 41% (19-64) 63% (41-85) 12 21% (0.1-41) 42% (18-66) Median, months 4.4 (2.6-8.0) 10.9 (3.9-21.0) Lower 95%CI for all 6-month PFS-rates exceed the pre-specified 15% minimum rate. 13% patients survived ≥18 months. 23% patients did not progress <12 months
Conclusion:
The toxicity rate was higher compared to that in fitter patients, but afatinib seems to improve PFS and OS in unfit EGFR-mutant NSCLC, and in suspected-positive patients who would otherwise only receive best supportive care.
