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L. Moreau
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MO08 - NSCLC - Early Stage (ID 117)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:K. Nakagawa, J. Douillard
- Coordinates: 10/28/2013, 16:15 - 17:45, Bayside Gallery B, Level 1
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MO08.02 - Adjuvant pazopanib or placebo in resected stage I NSCLC patients: results of the NSCLC adjuvant randomized phase II trial (IFCT-0703) from the French collaborative Intergroup (ID 2274)
16:20 - 16:25 | Author(s): L. Moreau
- Abstract
- Presentation
Background
Although UFT is approved in eastern countries, most guidelines do not recommend any adjuvant treatment in resected Stage I NSCLC. Pazopanib (P) is a potent, orally active multi-target receptor tyrosine kinase inhibitor of VEGFR-1, -2, -3, platelet derived growth factor (PDGFR) type-α and –β, approved in metastatic renal cell carcinoma and sarcoma. Neoadjuvant P demonstrated single-agent activity in patients with early stage NSCLC. We report the feasibility and tolerance of adjuvant P in stage I NSCLC.Methods
In this double-blind randomized multicenter phase II/III trial, completely resected patients (pts) with stage I NSCLC (7[th] TNM edition) were randomized to receive either placebo or P 800 mg/d during 6 months. The Fleming’s two stage phase II primary endpoint was compliance (i.e. % of pts able to receive at least 3 months of P, whatever the dose). After 64 pts included (interim analysis), IDMC recommended to start with P 400 mg/d because of initial insufficient compliance. A one-step Fleming design was used with the new dose. Phase II design was not comparative.Results
143 pts were randomized in 29 centers between March 2009 and August 2012, 71 and 72 in the placebo and P arms respectively. Most pts were male (61%) and smokers (91%), median age was 60. Pathological stage was IA in 111 pts (78%) and 16% were squamous cell carcinomas. Compliance for P800 was adequate in 38% (95% confidence interval [21-56]) vs. 87% [71-96] in placebo; for P400 in 69% [50-84] (p=0.01, compared to P800) vs. 93% [77-99] in placebo. Dose modifications were seen in 44% and 34% of P800 and P400 groups. The proportion of patient with at least one grade 3/4 toxicity was 53% [35-71] in P800 (13% [4-29] for placebo) and 38% [21-56] in P400 (27% [12-46] for placebo). No toxic deaths were observed. Only 2 pts has grade 4 toxicities in P800 (fatigue in P arm, GGT in the placebo arm). Most common toxicities G3 in P800 were diarrhea (9%), hypertension (9%), and increased transaminases (16% vs. 0% in P400); in P400 gastro-intestinal disorders (16%, 6% diarrhea) and hypertension (6%).Conclusion
IFCT-0703 is the first feasibility study demonstrating that full dose of P is safe but not feasible in the adjuvant setting in NSCLC. Compliance and tolerance with reduced dose appeared acceptable for adjuvant settings.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O18 - Cancer Control and Epidemiology II (ID 133)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Prevention & Epidemiology
- Presentations: 1
- Moderators:M.R. Spitz, L. Irving
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 103, Level 1
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O18.04 - Impact of Passive Smoking on molecular pattern in Never Smokers with Non-Small Cell Lung Cancer: Findings from the BioCAST / IFCT-1002 Study (ID 3305)
11:00 - 11:10 | Author(s): L. Moreau
- Abstract
- Presentation
Background
EGFR and HER2 mutations are usually associated with never-smokers while KRAS and BRAF mutations are thought to be link with smoking behavior in Non-Small Cell Lung Cancer (NSCLC). Passive smoking exposure is a well-known risk factor for lung cancer. Only EGFR and KRAS mutations were investigated in association with passive smoking and showed conflicting results. We aimed to investigate mutation rate of EGFR, HER2, KRAS, BRAF and ALK in a cohort of never smokers regarding their passive smoke exposure.Methods
The BioCAST / IFCT-1002 study is a prospective cohort of NSCLC patients diagnosed in French never-smokers patients (less than 100 cigarettes in lifetime) between November 2011 and January 2013, Passive smoking exposure was evaluated through standardized questionnaire. We obtained biomarkers mutation results through routine testing. We used Fisher, Chi-square, median test and Mann-Whitney U test for comparisons as appropriate. We used logistic regression to calculate adjusted odds ratio for risk of each mutations.Results
Out of the 384 patients included in the BioCAST database, 334 (87.0%) had available data on passive smoking exposure. Among them, 219 patients (65.6%) were ever exposed to passive smoking in their lifetime. 198 (59.3%) reported a domestic exposure (122 during childhood at least) and 60 (18.0%) a workplace exposure. Result of at least one biomarker mutation was available in 313 patients (93.7%). including 128 EGFR mutations in 297 patients, 8/174 HER2 mutations, 18/256 KRAS mutations, 10/196 BRAF mutations, and 20/171 ALK gene rearrangements. We found no difference in mutation rate according to passive smoke exposure (cf. Table 1). There was no difference when comparing cumulative year of exposure, smoker-year or passive-pack year (as continuous variable) to the mutation rate, for any biomarker. When considered as categorical variable – after division in quartiles – we found also no difference. Results were similar when focusing on domestic (childhood versus adulthood included) and workplace exposure only. Finally, we found no significant increased risk for mutation for any biomarker in logistic regression adjusted for most of other lung cancer risk factors.EGFR Mt (n=297) HER2 Mt (n=171) KRAS Mt (n=256) BRAF Mt (n=196) ALK Fusion (n=171) % % % % % Overall exposure Never 46.5 3.5 6.7 5.9 13.0 Ever 41.3 5.1 7.2 4.7 11.1 Domestic exposure Never 45.8 2.9 7.7 6.4 11.1 Ever 41.3 5.7 6.6 4.2 12.0 Exposure at workplace Never 43.3 5.5 7.0 5.4 12.2 Ever 42.3 0 7.0 3.6 8.3 Total 43.1 4.6 7.0 5.1 11.7 Exposure in childhood Ever 40.5 3.0 6.5 2.7 14.7 Only in adulthood 42.6 10.3 6.8 6.7 7.5 Conclusion
Although we report the largest and more comprehensive study focusing on this topic, we found no significant difference in the biomarker mutation profile of NSCLC occurring in French never-smokers regarding their exposure to passive smoking as compared with the pattern of mutations described never-smoker patients with any passive smoking.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P3.09 - Poster Session 3 - Combined Modality (ID 214)
- Event: WCLC 2013
- Type: Poster Session
- Track: Combined Modality
- Presentations: 1
- Moderators:
- Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P3.09-018 - IFCT-0803 Trial: a phase II study of cetuximab, pemetrexed, cisplatin and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non squamous, non-small cell lung cancer (NSCLC): preliminary safety analysis (ID 3281)
09:30 - 09:30 | Author(s): L. Moreau
- Abstract
Background
Cisplatin-based chemotherapy and concurrent radiotherapy are the standard treatments for locally advanced unresectable NSCLC. New therapeutic combinations using molecular targeted drugs are needed. IFCT-0803 Trial is a phase II study evaluating the benefit of adding cetuximab to a combination of concomitant radio-chemotherapy with cisplatin and pemetrexed in patients with stage III, non-squamous NSCLC. Data on safety and tolerance during the first 16 weeks of treatment, available after the inclusion of the first 62 eligible patients, are presented.Methods
Based on a two-stage Simon approach, 106 patients will be included in IFCT-0803 trial. An interim analysis of the first 34 patients authorized the continuation of the study. Eligible patients receive conformal thoracic radiation with no elective nodal irradiation (66 Gy in 33 fractions, ICRU) along with cisplatin (75 mg/m[2]) and pemetrexed (500 mg/m[2]) on day 1 administered intravenously every 21 days for four cycles; weekly cetuximab (400 mg/m[2] for the first week, then 250 mg/m[2]) is added from the first week of therapy for a total of 12 doses. The primary objective is to assess the disease control rate at the 16[th] week, one month after treatment completionResults
62 patients were included (37 male, 56 years mean age), PS 0 = 39 and PS 1 = 23, ever smoker = 57, stage IIIA = 31 and IIIB = 31, adenocarcinoma = 50. Compliance for the first 62 patients included was as follows: Day 1 chemotherapy was administered to 100% of patients on cycles 1 and 2, to 98.4% on cycle 3 and to 96.6% on cycle 4. Radiotherapy protocol was respected: median was 33 for number of fractions, 66 Gy for total dose, 46 days for duration of treatment, 39 patients had a maximal toxicity of grade 3 and 6 of grade 4. Table 1 lists the number of patients for the main categories of toxicity.
* :One patient died consecutively to a subdural hematoma caused by a fall, he had a grade 4 thrombocytopenian=62 grade 1/2 grade 3 grade 4 anemia 32 4 0 neutropenia 24 20 5 thrombocytopenia 30 4 2* general toxicity 42 13 0 skin toxicity 51 9 0 digestive toxicity (nausea and vomiting) 42 6 0 esophageal toxicity 43 10 0 febrile neutropenia - 5 0 renal toxicity 4 3 0 neurologic toxicity 11 0 0 Conclusion
IFCT-0803 trial is ongoing, the end of the inclusions is scheduled for October 2013. This combination therapy is feasible without any unexpected side effects.
