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M. O’brien
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MTE18 - Perspectives in the Systemic Treatment of Small-Cell Lung Cancer (Ticketed Session) (ID 312)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Lehar 1-2
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MTE18.01 - Perspectives in the Systemic Treatment of Small-Cell Lung Cancer (ID 6572)
07:30 - 08:30 | Author(s): M. O’brien
- Abstract
- Presentation
Abstract:
Small cell lung cancer is the prototype of a smokers cancer and therefore with changing smoking patterns and decreasing prevalence of smoking this is a tumour that happily we are seeing less frequently. However the nature of the disease, the morbidity and suffering it causes, and the tantalising chemo and radiotherapy sensitivity of this tumour make it of great medical and academic interest to us. More attention is now given to the morphology of small cell lung cancer and the blurred boundary with large cell neuroendocrine tumours and non small cell lung cancer with neuroendocrine features. At the end of the EGFR mutation driven lung cancer natural history, small cell lung cancer appears once resistant has developed to EGFR mutation therapies. If we start from the early stage disease and look at radical approaches and how these have changed in the last 20 years we see that the gains made by systemic treatment have been stable while outcomes have been improved by intensive local and focused treatments in the form of prophylactic cranial irradiation and consolidation radiotherapy to the mediastinum. Small gains have also been made by the timing of radiotherapy both quickly after last chemotherapy or when given in a concurrent fashion. The Convert study has now given us a faster twice a day delivery with equal effectiveness and toxicity to a higher dose once daily schedule. Surgery has never really taken off as a widely used treatment for SCLC. For all the anecdotal cases who have been cured with combined treatment involving surgery, we will also remember those patients who have failed to recover or have delayed recovery from surgery and lost the window of opportunity for systemic treatment in a disease that can rapidly change from asymptomatic to very symptomatic. Despite little change in systemic therapies, it is important that what we have, we use well and to this end patients with SCLC should be carefully monitored during treatment for treatment induced neutropenia as this is readily treated and prevented by the use of GCSF which has become cheap and readily available in most countries. In addition SCLC was also one of the solid tumours that benefited from denosumab in the trials of patients with bone metastases and thus denosumab or zometa should be added to patients with SCLC who have bone metastases to decrease bone morbidity. Extensive stage small cell lung cancer is still a challenge and currently a graveyard for drugs development. The drugs that are looking promising are the PD-L1 inhibitors, although PD-L1 in itself does not appear to be a biomarker. Anti- PD1 and PD-L1 antibodies, while active in some cases of SCLC are not as broadly active as in NSCLC. Indeed it does not appear that PD-L1 expression on tumour cells is not a predictors of response. On could argue that the patients with SCLC who have a response to anti PD1 therapies may have heterogeneous disease and have areas of NSCLC which drive the response. It has always been thought that SCLC must be a problem of proliferation of abnormalities at the stem cell level. Indeed now it is no surprise that an anti DDL3 antibody (rovalpituzumab tesirine) is showing activity in relapsed disease – a situation where responses are few but results of trials are rapid. It also appears that DDL3 expression is a biomarker to predict response. Once again this biological pathway like the PD1 pathway, is unpatentable and thus we can expect a florry of antibodies targeting in and around these receptors on stem cells. The PARP inhibitors are again a group of drugs that held much promise but as yet have failed to deliver a treatment option at any point in the SCLC pathway. Further trials are ongoing. Positive benefits from radiotherapy in extensive stage as in limited SCLC, tells us that any treatment that can control a site of disease and can improve outcome, and suggests that removal of clones is important as either a form of debulking treatment or indeed these clones are a future source of resistance. Thus research on the treatment of oligometastatic sites either at presentation, residual after treatment or on relapse, as in the ongoing work in NSCLC (e.g the Saron study) may lead to future gains in survival. The biology of SCLC should be approached in the same way as NSCLC i.e. when disease relapses, rebiopsies should become the norm with as large a piece of tissue as possible. SCLC also sheds tumour cells into the circulation, which are a source of material for interrogation. Despite the negative trials, it is still rewarding to treat SCLC patients – for the rapid improvement in symptoms with treatment and the small but real group who get long term responses, in addition the rapid results makes this still an area for many more years of research.
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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 - 15:45 | Author(s): M. O’brien
- 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.
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P3.05 - Poster Session with Presenters Present (ID 475)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.05-006 - Anxiolytic Effect of Acupuncture in a Phase II Study of Acupuncture and Morphine for Dyspnoea in Lung Cancer and Mesothelioma (ID 4056)
14:30 - 15:45 | Author(s): M. O’brien
- Abstract
Background:
Anxiety is common in cancer patients. Treatments include psychological therapies, psychotropic drugs and complementary therapies including acupuncture. Evidence for acupuncture for treating anxiety in cancer patients is lacking.
Methods:
A single-centre, randomised phase II study of patients with non-small cell lung cancer (NSCLC) or mesothelioma assessed the use of acupuncture for control of dyspnoea. One-hundred and seventy-three patients were randomised to acupuncture alone (A), morphine alone (M) or the combination (AM). Acupuncture was administered at upper sternal, thoracic paravertebral, trapezius trigger points and thumb points (LI4). Manubrial semi-permanent acupuncture studs were inserted for patient massage when symptomatic. Arm A patients received rescue morphine.
Results:
There was no statistically significant difference in the dyspnea control rate between arms. Secondary outcomes included measures of anxiety. The trial population had high levels of anxiety and depression with all patients having depression hospital anxiety and depression (HAD) score of >7 and 71.5% having anxiety HAD score of >7. VAS relaxation improved in arms A (1.06 points) and AM (1.48 points) compared to arm M (-0.19 points; p<0.001). Of those patients whom were anxious at baseline (HAD anxiety > 7), 78% of arm AM, 52% of arm A and 38% of arm M achieved a 1.5 point improvement in VAS relaxation (chi-squared p=0.002). At 7 days, the Lar anxiety score improved in arm A (1.5 points), arm AM (1.2 points) with no change in arm M (0 points, p=0.003).
Conclusion:
Acupuncture has an anxiolytic effect seen on two scoring systems in this trial. Further research in this area is warranted.
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PL04a - Plenary Session: Immune Checkpoint Inhibitors in Advanced NSCLC (ID 430)
- Event: WCLC 2016
- Type: Plenary
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:J. Soria, C. Zhou
- Coordinates: 12/07/2016, 08:45 - 09:40, Hall D (Plenary Hall)
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PL04a.01 - Health-Related Quality of Life for Pembrolizumab vs Chemotherapy in Advanced NSCLC with PD-L1 TPS ≥50%: Data from KEYNOTE-024 (Abstract under Embargo until December 7, 7:00 CET) (ID 7153)
08:45 - 09:40 | Author(s): M. O’brien
- Abstract
- Presentation
Background:
In KEYNOTE-024 (NCT02142738), pembrolizumab provided superior progression-free survival (PFS) over platinum-based chemotherapy as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression on ≥50% of tumor cells (ie, PD-L1 tumor proportion score [TPS] ≥50%) and no sensitizing EGFR or ALK aberrations (HR 0.50, P < 0.001). Despite a 44% crossover rate from chemotherapy to pembrolizumab, pembrolizumab also significantly improved overall survival (OS) (HR 0.60, P = 0.005). Any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related adverse events were less frequent with pembrolizumab. Health-related quality of life (HRQoL) is an important consideration for anticancer therapy, particularly in the first-line setting. We present data from the prespecified exploratory patient-reported outcomes (PRO) analysis of KEYNOTE-024.
Methods:
305 patients were randomized to pembrolizumab 200 mg Q3W or investigator-choice platinum-doublet chemotherapy plus optional pemetrexed maintenance therapy for nonsquamous disease. The EORTC QLQ-C30 and QLQ-LC13 were administered at cycles 1-3 and every 9 weeks thereafter. The key PRO end points were change from baseline to week 15 in the QLQ-C30 global health status/QoL score and time to deterioration in the QLQ-LC13 composite of cough, chest pain, and dyspnea. PROs were analyzed for all patients who received study treatment and completed ≥1 PRO instrument (n = 299).
Results:
Across treatment arms, PRO compliance was >90% at baseline and ~80% at week 15. Least squares (LS) mean (95% CI) change from baseline to week 15 in QLQ-C30 global health status/QoL score was 6.95 (3.29 to10.58) for pembrolizumab (n = 151) and –0.88 (–4.78 to 3.02) for chemotherapy (n = 148). The difference in LS means was 7.82 (95% CI 2.85-12.79; nominal 2-sided P = 0.002). The proportion of improved global health status/QoL score at week 15 was 40.0% for pembrolizumab and 26.5% for chemotherapy. Fewer patients in the pembrolizumab arm had deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30% vs 39%), and time to deterioration was also prolonged with pembrolizumab (HR 0.66, 95% CI 0.44-0.97; nominal 2-sided P = 0.029).
Conclusion:
Pembrolizumab was associated with a clinically meaningful improvement in HRQoL compared with platinum-based chemotherapy. Combined with the superior PFS and OS and manageable safety profile, these data suggest pembrolizumab may be a new standard of care for first-line treatment of PD-L1–expressing advanced NSCLC.
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