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B. Gao
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-033 - Patterns of Progression and Management of Acquired Resistance to Anti-PD-1 Antibodies in Advanced Non-Small Cell Lung Cancer (ID 6285)
14:30 - 14:30 | Author(s): B. Gao
- Abstract
Background:
Anti-PD-1 antibodies (pembrolizumab and nivolumab) have shown improved overall survival in second-line treatment for metastatic non-small cell lung cancer (NSCLC) with durable responses. We aimed to assess the pattern of disease progression amongst patients who initially responded to anti-PD-1 agents and their subsequent management.
Methods:
We retrospectively assessed all patients who commenced single-agent anti-PD-1 antibodies between June 2012 and February 2016 at a single centre. Radiological responses were assessed by the investigator using RECIST 1.1 and irRC. Progressive disease (PD) patterns were defined as solitary, oligometastatic (2-3 lesions), generalised (>3 lesions), enlargement of existing or new lesions, visceral or non-visceral. Management and survival after progression were examined.
Results:
A total of 81 patients received single-agent pembrolizumab (N=43) or nivolumab (N=38). Of the seventeen (21.3%) patients achieving partial response, three were treatment-naïve, fifteen (88.2%) were former or current smokers, none had EGFR mutation or ALK translocation. The median number of disease sites at baseline was three, and two patients had stable brain metastases after radiotherapy at the commencement of anti-PD1 treatment. Ten (58.8%) responders developed acquired resistance, with a median time to progression of 20.2 months. Nine (90%) had solitary (N=4) or oligometastatic (N=5) progression. Five (50%) progressed only at existing sites, three (30%) developed new lesions only, and two (20%) progressed at both existing and new sites. Four (40%) progressed at non-visceral sites only, and one progressed in the brain at a previously treated site. Five (50%) patients underwent local treatment to solitary (N=2) or oligoprogressive disease (N=3) with all five achieving local control with radiotherapy. Seven(70%) continued anti-PD-1 agents beyond progression, while the three (30%) remaining patients did not receive any further therapy. With a median follow-up of 24.8 months, five (50%) of the patients had died, one from an infective exacerbation of COPD, one from type 1 respiratory failure, and three from disease progression. The median duration of treatment was 4.35 months (1.96 to 11.46) and the median overall survival after progression was 11.44 months.
Conclusion:
This study suggested that acquired resistance to anti-PD1 agents could often result in solitary or oligometastatic progression, and that CNS progression was uncommon. In a subset of patients, treatment beyond progression with or without local therapy to oligometastatic disease may provide ongoing and durable clinical benefit.
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P3.02c-055 - Incidence and Grade of Pneumonitis in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Anti-PD-1 Antibodies (ID 4538)
14:30 - 14:30 | Author(s): B. Gao
- Abstract
Background:
Advanced non-small cell lung cancers (NSCLC) can be treated with anti-PD1 (programmed cell death 1) antibodies. Anti-PD-1 therapy can lead to immune mediated adverse events. This study examines the incidence of pneumonitis, a potentially fatal complication, in patients with advanced NSCLC treated with anti-PD-1 antibodies at 3 large hospitals in Sydney, Australia.
Methods:
NSCLC patients commenced on pembrolizumab (2 mg/kg or 10 mg/kg Q3W) or nivolumab (3 mg/kg Q2W) were assessed for adverse events including pneumonitis. Patient demographics, treatment history and immune mediated complications were collected. Pneumonitis was graded according to the Common Terminology Criteria for Adverse Events Version 4.0. Pneumonitis treatment and clinical outcomes were collected. Serial imaging was reviewed with a blinded radiologist.
Results:
A total of 104 patients between 2012 and 2016 were treated with anti-PD-1 therapy. Median age for included patients was 67. Fourteen (14%), 35 (34%), and 53 (51%) had anti-PD-1 as first, second, or third and subsequent line treatment respectively. Nine patients (9%) developed pneumonitis. Three patients (4%) developed grade 3 (G3) or higher pneumonitis including one patient (1%) that died due to pneumonitis. All patients with ≥G3 pneumonitis required hospital admission with one requiring admission to a high dependency unit. None of the patients with ≥G3 pneumonitis were retreated with anti-PD1 therapy. All patients with ≥G3 pneumonitis died within 5 weeks of their diagnosis of pneumonitis. Seven patients with pneumonitis were treated with steroids. The median length of treatment with steroid was 29 days. Pneumonitis involved both lungs in 3 patients. Of the remaining 6 patients – 2 had all right lung lobes involved, 2 had two lobes and 1 had one lobe. Fifteen (14%) patients had a history of receiving concurrent chemoradiotherapy prior to anti-PD-1 therapy. A further 6 (6%) had curative intent radiotherapy and 15 (14%) had palliative radiotherapy to the thorax prior to anti-PD1 therapy. One of the patient with G3 pneumonitis had previously received radiotherapy to the chest. No association between prior radiotherapy and pneumonitis was seen.
Conclusion:
The incidence of pneumonitis is rare but our real-life multi-institutional experience demonstrates an incidence higher than reported in the literature. This complication can be life threatening and onset of ≥G3 pneumonitis is associated with short survival.
