bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased antiresorptive activity of zoledronic acid (Z) administered in the night as compared to morning administration in breast cancer (BC) patients with bone metastases
Authors: Bottini A. , Generali D. , Berruti A. , Tampellini M. , Torta M. , Tedoldi S. , Bonardi S. , Tucci M. , Gorzegno G. , Dogliotti L. 
Published: March 2020

677

Background:
Z is an effective bisphosphonate in preventing skeletal related events (SREs) in bone metastatic patients. Decrease in bone resorption markers during Z therapy is a potential surrogate of drug efficacy. Bone resorption markers maintain a circadian rhythmicity in metastatic BC patients (Generali et al ASCO 2005), suggesting that Z may be more active if administered in a chronomodulated way. Raised PTH after Z could impair the drug efficacy (Berruti et al ASCO 2006).
Methods:
Forty-four BC patients with bone metastases were randomised to receive Z, 4 mg i.v. at 11.00 p.m or 11 a.m every 28 days for 4 times. Serum cross laps (CTX), urinary n-telopeptide (NTX) and serum parathyroid hormone (PTH) levels were measured at baseline and after 4, 7, 14, 28, 56 and 84 days, respectively.
Results:
Z administration in the night resulted in a greater decrease of either serum CTX or urinary NTX and lower increase in serum PTH (
Table
) than morning administration.
Conclusions:
Z administration in the night might be more efficacious than morning administration.

Treat
baseline
Day 4
Day 7
Day 14
Day 28
Day 56
Day 84

p
*

CTX ng/ml

day
0.77 (0.09)
0.09 (0.02)
0.10 (0.01)
0.13 (0.02)
0.16 (0.03)
0.16 (0.02
0.17 (0.02)
<.05

night
0.72 (0.09)
0.09 (0.02)
0.07 (0.01)
0.10 (0.02)
0.12 (0.03)
0.10 (0.02)
0.08 (0.02)

NTX nmol/mmol creatinine

day
164.4 (28.1)
32.2 (6.6)
33.5 (6.1)
50.7 (8.7)
60.9 (9.4)
53.4 (8.9)
45.8 (8.0)
<.05

night
138.7 (26.6)
36.4 (6.3)
40.0 (5.8)
44.0 (8.2)
39.3 (8.9)
33.6 (8.5)
46.3 (7.6)

PTH ng/ml

day
40.3 (17.3)
106.3 (17.5)
120.8 (19.3)
102.7 (20.9)
88.4 (18.5)
148.6 (49.3)
95.8 (27.5)
<.0001

night
52.7 (16.0)
66.3 (16.2)
65.1 (17.9)
61.3 (19.4)
55.5 (17.2)
63.5 (45.6)
48.4 (25.4)

Data are mean (standard error)

*
Mixed random effect model of multivariate analysis of variance

No significant financial relationships to disclose.
Randomized phase II trial of cisplatin/gemcitabine with or without LY293111, a multiple eicosonaid pathway modulator, in patients with chemotherapy naïve advanced non-small cell lung carcinoma
Authors: Janne P. A. , Paz-Ares Rodriguez L. , Gottfried M. , Reaume M. N. , Kaukel T. , Oh Y. W. , Sykes A. , Enas N. , Brail L. H. , Von Pawel J. 
Published: March 2020

7024 Background: The eicosanoid pathway is altered in NSCLC. Pharmacological activators of peroxisome proliferator-activated receptor-gamma (PPARγ) have been shown to inhibit lung tumors in vitro. LY293111 inhibits the eicosanoid pathway, is a PPARγ agonist and modulates adipophilin and adiponectin expression levels in vitro. LY293111 is well tolerated and can be administered with cisplatin/gemcitabine. A randomized phase II study in NSCLC was undertaken. Methods: Pts with stage IIIB/IV NSCLC were randomized to two doses of LY293111 (200 mg BID (Arm A) or 600 mg BID (Arm B) or placebo (Arm C) alone for 7 days followed by concurrent cisplatin (75 mg/m2;d1) and gemcitabine (1250 mg/m2;d1,8) q21 days. Treatment was continued until disease progression or toxicity. Primary endpoint was PFS with 75% power to detect 33% improvement compared to placebo (5 months). Calculated sample size was 65 pts/arm (195 total) with a one sided type I error of 0.2. Changes in adipophilin mRNA expression and adiponectin serum levels were assessed at baseline and day 7. Results: Between 09/03 and 07/04, 201 pts were randomized and 195 treated. Demographics (all pts): M:F (65%:35%); median age 61 (range 27–87); stage IIIB/IV (15%:85%); ECOG PS (0:36%;1:64%). Demographics were well balanced between the 3 arms. Most common CTC grade 3/4 toxicities were nausea (8%), vomiting (7%), fatigue (6%) and diarrhea (6%) with only diarrhea related to dose of LY293111 (p=0.03). Response rates (CR+PR) were similar in all 3 arms (A:20%; B:27%; C:21%). There was no significant difference in median PFS (95% CI) between the arms (A: 4.6 months (3.2–5.0); B:6.0 months (4.6–7.2); C:6.0 months (5.2–7.0)). Median survival (95% CI) was similar in all 3 arms (A: 7.3 months (6.2–9.4); B:7.9 months (7.2–9.7); C: 9.0 months (7.7–12.5). Median change in serum adiponectin levels at d7 were significantly higher in arm B vs. placebo (p < 0.05). Adipophilin expression at d7 was increased in a dose dependent manner (p=NS) in arms A and B vs. placebo. Conclusions: LY293111 in combination with cisplatin/gemcitabine did not increase median PFS compared to placebo in pts with NSCLC. Pharmacodynamic modulation was observed but did not impact efficacy. [Table: see text]
Sequencing of single-agent (SA) docetaxel (T) and gemcitabine (G) therapy for patients (pts) with advanced non-small cell lung cancer (NSCLC): Results of three consecutive randomized trials
Authors: Manegold C. , Thatcher N. , Kortsik C. , Koschel G. , Mezger J. , Schott Von Römer K. , Pilz L. R. 
Published: March 2020

7035 Background: Standard doublet chemotherapy (DCT) is often clinically inappropriate. Since T and G show efficacy and favourable toxicity as SAs in 1st- and 2nd-line setting, sequencing of T and G may be an equally effective alternative to DCT for palliation. Three studies (S1-S3) were conducted: two to identify an optimal SA-sequence (S1/S2), and one to compare sequential SA to a platin-free doublet (S3). Methods: Common eligibility criteria included histologically confirmed stage IIIB or IV, performance status (PS) 0–2, and no prior chemotherapy. S1/S2 examined treatment feasibility (TF) of G or T with introduction of the opposite agent in case of progression. TF was defined as pt ability to receive ≥2 cycles (cyc) of 1st-line and if progressive ≥2 cyc of 2nd-line therapy and to survive ≥7 months (mos). In S1, G 1000 mg/m2 and T 35 mg/m2 was given on days (d) 1, 8, 15 (q4w) and in S2, G 1250 mg/m2 (d 1, 8) and T 100 mg/m2 (d 1; q3w). In S3, pts received G 1000 mg/m2 (d 1, 8) and T 75 mg/m2 (d 1; q3w) either concomitantly (G+T; 6 cyc) or sequentially (G→T; 3 cyc each). Primary endpoint of S3 was clinically relevant haematotoxicity (CRHT) defined as thrombocytopenia with platelet transfusions, anaemia with RBC-transfusions or febrile neutropenia with i.v. antibiotics (IVAB). Results: 819 pts were included (1998–2004): 85% of pts had stage IV disease and PS≤1. In S1 and S2 for (G→T)/(T→G) respectively: TF was 28/20% and 38/49% (p=.04); median survival (MS) was 9.0/5.0 mos (p=.03) and 6.3/8.6 mos; and median time to progression (TTP) was 4.3/2.2 mos and 2.4/3.3 mos. In S3, CRHT occurred less frequently with SA therapy (p<.001), transfusions and IVAB treatment days were less common. QoL also favoured SA therapy. For (G+T)/(G→T), MS was 7.3/7.4 mos, response rate was 33/22% (p=.05) and TTP was 6.3/4.9 mos (p=.04). Conclusions: Sequencing modern SA was effective and well tolerated. Weekly T and G regimens seem less feasible than 3-weekly but compared to the nonplatinum doublet CRHT and IVAB are reduced with better QoL and cost-effectiveness. [Table: see text]
Two consecutive phase 1–2 studies of cisplatin (P)-based 1st-line chemotherapy (CT) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC). The MILES-2P studies
Authors: Perrone F. , Illiano A. , Piantedosi F. V. , Bearz A. , Favaretto A. , Lorusso V. , Manzione L. , Iaffaioli R. V. , Valerio M. R. , Gridelli C. 
Published: March 2020

7037 Background: P-based CT needs prospective testing in elderly pts with advanced NSCLC. In two consecutive studies, with equal design, feasible dose of P combined with gemcitabine (PG) or vinorelbine (PV) were identified and toxicity and activity were described. Methods: Advanced (stage IV or IIIb with supraclavear nodes or pleural effusion) NSCLC pts, aged >70 years, PS 0–1, were eligible. P was given on day (d) 1, starting dose-finding at 50 mg/m2 (level 0), with G (fixed dose: 1000 mg/m2 dd 1&8) or V (fixed dose: 25 mg/m2 dd 1&8); at each level <2 unacceptable toxicities in cycle 1–3 (UT) out of 6 evaluable pts were needed to escalate; CT was given every 3 weeks, up to 6 cycles. A two-stage flexible optimal design was applied at the feasible dose. With rate of pts without UT as endpoint, type I and II error =0.10, p0=0.70, p1=0.85, ≥47 pts without UT out of 60 enrolled were required at the final stage. NCI-CTC for toxicity and RECIST for response coding were used. Results: From June 2002 to November 2004, 159 pts were enrolled (38 in dose-finding and 121 in phase 2); 45% of them were aged ≥75. P was feasible at 60 mg/m2 (level +1) with G, and 40 mg/m2 (level -1) with V. With PG (n=60): 50 (83%) pts without UT; response rate (RR): 43%, 95% exact CI: 31–57; median progression-free (PFS) and overall survival (OAS): 25 and 44 wks, respectively. Toxicity (≥5% of pts): g3 anemia (5%), RBC transfusion (8%), g3–4 platelets (10%), g2–3 cardiac (10%), g2 renal (7%). With PV (n=61): 50 (82%) pts without UT, 2 toxic deaths (1 with febrile neutropenia [FN] and 1 with cardiac toxicity); RR 36%, 95% exact CI: 24–49; median PFS and OAS: 21 and 33 wks, respectively. Toxicity (≥5% of pts): g3 anemia (5%), RBC transfusion (8%), FN (5%), g≥2 neurologic (5%). Conclusions: The combination of cisplatin and gemcitabine (with P 60 mg/m2) is safe, active, and deserves comparison vs single-agent chemotherapy in elderly pts with advanced NSCLC. No significant financial relationships to disclose.
Stereotactic hypofractionated high-dose irradiation (STI) for stage I non-small cell lung cancer (NSCLC): Mature results in 300 cases of a Japanese multi-institutional study
Authors: Onishi H. , Nagata Y. , Shirato H. , Karasawa K. , Gomi K. , Hiraoka M. , Kimura T. , Hayakawa K. , Kokubo M. , Takai Y. 
Published: March 2020

7045 Background: With the increasing accuracy of localization for tumor-bearing areas using various new techniques, hypofractionated or single high-dose stereotactic irradiation (STI) has been actively investigated for stage I NSCLC in Japan. The current study retrospectively evaluated Japanese multi-institutional results for high-dose STI for stage I NSCLC. Methods: From 1993 to 2003, stereotactic three-dimensional treatment was performed using 3–10 non-coplanar dynamic arcs or 6–20 static ports for a total of 300 stage I (median age, 75 years; T1N0M0, n = 193; T2N0M0, n = 107) patients with primary NSCLC (adenocarcinoma, n = 138; squamous cell carcinoma, n = 129; and others, n = 33) in 14 institutions. Totally 190 patients were medically inoperable, and other 110 were medically operable but selected STI. A total dose of 18–75 Gy at the isocenter was administered in 1–22 fractions. Median calculated biological effective dose (BED) was 108 Gy (range, 57–180 Gy). Results: Median follow-up period of survivors was 38 months (range; 2–128 months). Pulmonary complications of NCI-CTC criteria (version 2.0) grade ≥ 3 were noted in 9 patients (3.0%). Local progression occurred in 44 patients (14.7%), and 5-year local control rate was high (86%) for BED ≥100 Gy (n = 227) compared to 67% for <100 Gy (n = 73) (P < 0.001). Overall 5-year survival rates of operable and inoperable patients were 65% and 37%, respectively. Overall 5-year survival rates in operable cases was high (74%) for BED ≥100 Gy (n = 85) compared to 37% for <100 Gy (n = 24) (P < 0.01). In a subset of operable patients irradiated with BED ≥100, 3-year locally progression-free survival rates was high (81%) for stage IA (n = 60) compared to 67% for stage IB (n = 23) (P < 0.05) Conclusions: Local control and survival rates of STI for stage I NSCLC are better with BED ≥100 Gy compared to <100 Gy. Survival rates in selected patients (medically operable, BED ≥100 Gy) were excellent, and potentially comparable to those of surgery. Stage IB patients displayed higher rate of local progression than stage IA. We have started multi-institutional prospective study for stage IA NSCLC with a schedule of total dose of 48 Gy in 4 fractions during 4–8 days. No significant financial relationships to disclose.
Induction (ICT) or consolidation chemotherapy (CT) with cisplatin (C) and paclitaxel (P) plus concurrent chemo-radiation (CT/TRT) with cisplatin and vinorelbine (V) for unresectable non-small cell lung cancer (NSCLC) patients (pts): Randomized phase II trial GFPC-GLOT-IFCT 02–01
Authors: Fournel P. , Vergnenégre A. , Robinet G. , Léna H. , Gervais R. , Le Caer H. , Souquet P. J. , Chavaillon J. M. , Chouaid C. , Martel-Lafay I. 
Published: March 2020

7048 Background: Concurrent CT/TRT is the standard treatment for unresectable stage III NSCLC, but the optimal sequencing of TRT and CT is not well defined.Consolidation CT with taxane seems to be a good approach (SWOG 95–04). Methods: Unresectable stage III NSCLC pts (weight loss < 10%, ECOG PS 0–1, no supraclavicular lymph node or superior vena cava syndrome) were eligible. in Arm A, pts received 2 cycles of C 80 mg/m2 and P 200 mg/m2 followed by a concurrent CT/TRT including TRT as 66 Gy in 33 fractions and C 80 mg/m2 d1,29 and 57 and V d1,8,29,36,57 and 64. In Arm B, the same CT/TRT began on d1 followed by 2 cycles of C and P. The primary objective was response rate at the end of treatment, assessed by RECIST criteria. 132 pts were needed. Results: From 05/2002 to 03/2005, 133 pts were included by 35 centers. 5 pts were ineligible. Both groups were well-matched for baseline characteristics. 30 pts were stage IIIAN2 and 98 stage IIIB. Toxicities (106 pts analyzable) grade 3–4 by CTC and RTOG criteria (Arm A/Arm B) were: neutropenia 36%/41%, infection 11%/15%, esophagitis 6%/13%, pneumonitis 0%/1%. 5 toxic deaths were observed (2 sepsis, 1 massive hemoptysis, 1 post-irradiation pneumonitis, 1 esophageal fistula). In Arm A, objective response rate was 36% after ICT. At the end of treatment, response rate (Arm A/Arm B) was in intent to treat: progression 19%/19%, stable-disease 6%/11%, objective response 55%/48%. 13 pts were not evaluable for response in Arm A and 14 in Arm B [ table ]. Conclusions: Toxicities and response rates are similar in both arms, but ICT followed by CT/TRT appears to provide a better therapeutic outcome. [Table: see text] No significant financial relationships to disclose.
Prospective evaluation of RRM1 as a predictor of response to gemcitabine/carboplatin (GC) in non-small cell lung cancer (NSCLC)
Authors: Bepler G. , Sharma A. , Greenberg H. , Cantor A. , Li X. , Hazelton T. , Walsh F. , Simon G. 
Published: March 2020

7054 Background: RRM1 is the regulatory subunit of ribonucleotide reductase. It is a molecular target of G. RRM1 increases upon continuous exposure of cell lines to G. Preliminary data suggest improved survival for patients with low as opposed to high tumoral expression of RRM1 when treated with G-based chemotherapy. Methods: We determined the efficacy of G and C as induction therapy in patients with locally advanced NSCLC. Trial eligibility included measurable disease, no prior chemotherapy or RT, PS 0–1, and no weight loss. Patients were staged with CT, PET, and brain MRI. GC consisted of two 28-day cycles of G, 1,000 mg/m2 d1&8 and C, AUC 5 d 1. Unidimensional tumor measurements were obtained before and after GC. The study required tumor collection prior to therapy by core needle biopsy. Specimens were frozen in LN. Tumor cells were collected by LCM. Real-time quantitative RT-PCR gene analysis was performed in triplicate per sample for RRM1 and 18SrRNA. Results: Between 11/03 and 7/05, 30 eligible patients were enrolled, and the required tumor biopsies were obtained in all. In one patient, a pneumothorax developed that required chest tube placement. Disease response ranged from a 9% increase to a 100% decrease. 14/26 had SD, 11/26 PR, and 1/26 CR. The patients’ age was 47- 87 years; 12 were women; 13 had IIIA and 13 IIIB; 10 had sq, 7 ad, and 9 LC or NOS NSCLC. RRM1 expression ranged from 0.18 to 129.3. There was a significant (p = 0.014) inverse correlation (r = −0.474) between RRM1 expression and disease response. When grouping patients into those with response (CR/PR) and without response (SD), RRM1 expression was significantly (p = 0.027) associated with response. No significant association was found between RRM1 expression and other parameters. Conclusions: In a prospective clinical trial intratumoral RRM1 expression was significantly and inversely correlated with disease response to gemcitabine and carboplatin. These results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine-based chemotherapy. No significant financial relationships to disclose.
Prospective FDG-PET and CT assessment of discontinuation of erlotinib (E) or gefitinib (G) in patients with EGFR TKI sensitive non-small cell lung cancer (NSCLC) who subsequently progress radiographically on E or G (“acquired resistance”) followed by re-initiation of E or G and the subsequent addition of everolimus (RAD001)
Authors: Riely G. J. , Kris M. G. , Schwartz L. H. , Akhurst T. , Zhao B. , Milton D. T. , Moore E. , Tyson L. , Pao W. , Miller V. A. 
Published: March 2020

7065 Background: About 10% of patients (pts) with NSCLC have a radiographic response to E or G. A dependence on signaling through the epidermal growth factor receptor (EGFR) is thought to underlie this response. Despite initial regression, these pts invariably develop acquired resistance to E or G. Optimal management of these patients is unknown. In patients with acquired resistance, we sought to evaluate changes in tumor metabolism by PET and size by CT after discontinuation of E or G, resumption of E or G, and then the addition of the mTOR inhibitor everolimus to E or G. Methods: Pts with stage IV NSCLC with exon 19 or 21 EGFR mutation or previous radiographic response after treatment with E or G and then radiographic progression after > 6 months of treatment were eligible. All pts had 4 FDG-PET/CT and helical CT scans: baseline, 3 weeks after discontinuation of E or G, 3 weeks after restarting E or G, and 3 weeks after combined treatment with everolimus (5 mg daily) and E or G. CT measurements were uni-dimensional. Results: To date, 9 pts (5 on G, 4 on E) have enrolled with 6 pts completing all 4 PET/CT and CT assessments. Within 3 weeks of discontinuation of E or G, 7 of 9 (77%, 95% CI 40–97%) developed symptomatic disease progression. Three of 6 pts had an increase in SUV of >50% and increase in CT measurements >15% 3 weeks after discontinuation of E or G. Three of 6 pts had decrease in SUV of >10% 3 weeks after resumption of E or G. Two of 6 pts had further reduction of SUV > 50% and >10% decrease in CT measurements 3 weeks after everolimus was added to E or G. Conclusions: In EGFR TKI-sensitive patients who develop acquired resistance: 1) Discontinuation of E or G results in rapid symptomatic progression and increases in SUV on PET of indicator lesions. 2) Both symptoms and SUV values improve on re-initiation of E or G, suggesting that some tumor cells remain sensitive to EGFR blockade. 3) We saw further improvement when everolimus was combined with E or G. Based on these data we now recommend continuing E or G in similar patients. Support: Novartis, CA05826, MSKCC “Steps for Breath.” [Table: see text]
A factorial phase III randomized trial of rofecoxib and prolonged constant infusion of gemcitabine at 10mg/m2/min (PCI-G) in first-line treatment of adult patients (pts) with advanced non-small cell lung cancer (NSCLC): The GECO study
Authors: Gridelli C. , Ceribelli A. , Gebbia V. , Gamucci T. , Ciardiello F. , Carrozza F. , Favaretto A. , Daniele B. , Galetta D. , Morabito A. 
Published: March 2020

7069 Background: Preclinical and clinical evidence suggest that rofecoxib and PCI-G might improve efficacy of treatment of advanced NSCLC. Methods: Advanced (stage IV or IIIb with supraclavear nodes or pleural effusion) NSCLC pts, aged <70, PS 0–1, were eligible. A 2x2 factorial design was applied to test if addition of rofecoxib (50 mg daily) or PCI-G could improve overall survival (OAS) compared with standard first-line treatment [cisplatin (80 mg/m2 d 1) and gemcitabine (1200 mg/m2 dd 1&8) every 21 days]. To have 80% power of detecting a 0.67 HR of death, with bilateral alpha = 0.05, 400 pts were planned and 200 deaths were required for each comparison. Response was assessed with RECIST, quality of life (QoL) by EORTC questionnaires. Results: From Jan ’03 to May ’05, 400 pts were enrolled. Rofecoxib arms were closed (Oct 1st,’04) due to manufacturer decision of drug withdrawing for safety issues. As of Dec ’05, analyses include 400 pts (246 deaths) for PCI-G and 240 pts (enrolled as of Jul 1st,’04 to have a 3-month chance of treatment) for rofecoxib comparison (168 deaths). Median age was 60. PCI-G did not improve OAS (median 47.3 vs 42.9 weeks with standard infusion, HR 0.97, 95% CI 0.75–1.25), nor any other secondary end-point. Rofecoxib did not prolong OAS (median 43.6 vs 44.1 weeks without rofecoxib, HR 1.01, 95% CI 0.74–1.38), but improved response rate (41.2% vs 26.4%, p = 0.02), global QoL, physical and role functioning, fatigue, pain and analgesic consumption. In both comparisons, there was no clinically relevant difference in toxicity. Conclusions: Neither PCI-G nor rofecoxib prolonged OAS. Rofecoxib improved response rate and several QoL items, including pain-related and global QoL. Partially supported by AIRC; rofecoxib freely supplied by MS&D Italy. No significant financial relationships to disclose.
Independent review of fatal interstitial lung disease (ILD) in TRIBUTE: paclitaxel + carboplatin ± erlotinib in advanced non-small cell lung cancer (NSCLC)
Authors: Gandara D. R. , Yoneda K. , Shelton D. , Beckett L. A. , Ramies D. A. , Bloss J. , Herbst R. S. 
Published: March 2020

7071 Background: ILD is a rare but serious complication of EGFR tyrosine kinase inhibitor (TKI) therapy, fatal in about 1/3 of cases. The incidence, severity & risk factors for ILD remain poorly understood, but it is reported to be more common in Asian patients receiving gefitinib. Whether the risk of ILD with gefitinib exceeds that of erlotinib is unclear. Whether concurrent chemotherapy increases the risk of ILD is also unclear. Methods: This study was designed to determine the incidence of ILD leading to death in 1,059 TRIBUTE patients randomized to chemotherapy plus erlotinib or placebo (Herbst: JCO, 2005). A blinded review of fatal SAEs was performed by an independent 3 person panel comprised of a medical oncologist (DRG), radiologist (DS), and pulmonologist (KY) unassociated with the study. Fatal respiratory SAEs (41 met criteria) were assigned to 1 of 4 potential attributions: progressive NSCLC; concurrent illness; toxicities not related to study drug; or ILD. Each panel member first made an independent assignation based on case report forms/source documents; then each case was discussed jointly. If needed, consensus was reached by vote. Results: Fatal SAEs were reported in 80/1059 patients (7.6%): 53/526 patients on erlotinib (10.1%) & 27/533 on placebo (5.1%) (p = 0.002). Consensus assignation for 41 respiratory SAEs was as follows: NSCLC: 18 (44%), concurrent illness: 15 (37%), toxicities not related to study drug: 5 (12%), ILD: 3 (7%). There were no statistical differences in assignation by study arm. However, all 3 ILD cases occurred in the erlotinib arm (3/523; overall incidence 0.6%). Case details will be provided. Conclusions: 1) To our knowledge, this analysis of TRIBUTE is the only independent blinded assessment of respiratory SAEs & ILD related to an EGFR TKI (erlotinib) + chemotherapy. 2) Overall, there were 41 fatal respiratory SAEs (3.9%). Fatal ILD occurred in 0.6% of cases treated with the combination. Using estimates that 1/3 of EGFR TKI-induced ILD cases are fatal, the overall incidence in this study arm was likely around 1.5–2%, not inconsistent with prior reports of TKIs alone. 3) Further studies designed to better define the underlying pathophysiology and risk factors for ILD are needed. [Table: see text]