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Background The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. Methods The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. Results The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. Conclusions Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy.

Summary Background Atezolizumab (a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapy as first-line treatment of non-small-cell lung cancer. IMpower130 aimed to assess the efficacy and safety of atezolizumab plus chemotherapy versus chemotherapy alone as first-line therapy for non-squamous non-small-cell lung cancer. Methods IMpower130 was a multicentre, randomised, open-label, phase 3 study done in 131 centres across eight countries (the USA, Canada, Belgium, France, Germany, Italy, Spain, and Israel). Eligible patients were aged 18 years or older, and had histologically or cytologically confirmed stage IV non-squamous non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and received no previous chemotherapy for stage IV disease. Patients were randomly assigned (2:1; permuted block [block size of six] with an interactive voice or web response system) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin [area under the curve 6 mg/mL per min every 3 weeks] plus nab-paclitaxel [100 mg/m2 intravenously every week]) or chemotherapy alone for four or six 21-day cycles followed by maintenance therapy. Stratification factors were sex, baseline liver metastases, and PD-L1 tumour expression. Co-primary endpoints were investigator-assessed progression-free survival and overall survival in the intention-to-treat wild-type (ie, EGFRwt and ALKwt) population. The safety population included patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02367781. Findings Between April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumab plus chemotherapy group (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapy group (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18·5 months [IQR 15·2–23·6] in the atezolizumab plus chemotherapy group and 19·2 months [15·4–23·0] in the chemotherapy group). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18·6 months [95% CI 16·0–21·2] in the atezolizumab plus chemotherapy group and 13·9 months [12·0–18·7] in the chemotherapy group; stratified hazard ratio [HR] 0·79 [95% CI 0·64–0·98]; p=0·033) and median progression-free survival (7·0 months [95% CI 6·2–7·3] in the atezolizumab plus chemotherapy group and 5·5 months [4·4–5·9] in the chemotherapy group; stratified HR 0·64 [95% CI 0·54–0·77]; p Interpretation IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumab plus chemotherapy versus chemotherapy as first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer. Funding F. Hoffmann-La Roche.

Aim: Evaluate real-world patient preferences, experiences and outcomes (health-related quality of life [HRQoL]) from patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) utilizing the ALKConnect Patient Insight Network. Patients & methods: Demographics, disease history/status/treatment, patient preferences and HRQoL (MD Anderson Symptom Inventory lung cancer module, reported as symptom severity and interference) were evaluated for US adults with ALK+ NSCLC. Results: Among 104 patients (median age: 53.0 years, 67.3% female, 40.0% employed), HRQoL and 3-month delay in disease progression were important treatment attributes. Burdensome symptoms included fatigue and disturbed sleep. Symptoms interfered most with work and day-to-day activity. Higher HRQoL was associated with ALK tyrosine kinase inhibitor (TKI) treatment and employment. Conclusion: ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC.

We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous NSCLC.Chemotherapy-naive patients with stage IV nonsquamous NSCLC without sensitizing EGFR or ALK genetic alterations were randomized in a one-to-one ratio to receive four or six cycles of carboplatin or cisplatin plus pemetrexed (PP) or APP every 3 weeks, followed by maintenance therapy with atezolizumab plus pemetrexed or pemetrexed alone. Co-primary end points were overall survival (OS) and investigator-assessed progression-free survival (PFS).The intention-to-treat population included 578 patients (APP, n = 292; PP, n = 286). At the primary PFS analysis (May 22, 2018; median follow-up, 14.8 mo), APP exhibited significant PFS improvement versus PP (median = 7.6 versus 5.2 mo, stratified hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.49-0.72, p0.0001). OS for the APP group was numerically better but not statistically significant at the interim (May 22, 2018; median = 18.1 versus 13.6 mo, stratified HR = 0.81, 95% CI: 0.64-1.03, p = 0.0797) and final analyses (July 18, 2019; median = 17.5 versus 13.6 mo; stratified HR = 0.86, 95% CI: 0.71-1.06, p = 0.1546). The OS and PFS results favored APP versus PP across subgroups. Grade 3 or 4 treatment-related adverse events occurred in 54.6% (APP) and 40.1% (PP) of patients; grade 5 treatment-related events occurred in 3.8% and 2.9%, respectively.IMpower132 met its co-primary PFS end point but not its co-primary OS end point, with numerical improvement for OS in the APP arm. APP had a manageable safety profile, with no new or unexpected safety signals identified.

Telemedicine has historically been underutilized in medicine broadly, and specifically in oncology, despite the general availability of the needed infrastructure to offer it as a platform for remote care. The COVID-19 pandemic posed new risks of infection exposure and potentially life-threatening complications, particularly in patients with cancer, created a new setting for cancer care ideally suited for the rapid roll-out of telemedicine for patients with cancer who need regular follow up but in whom live visits may not be critical. In the months since the upheaval of our health care system and wider society in the United States, as well as other countries, our early experience with telemedicine has demonstrated the feasibility of telemedicine for a subset of patients with cancer, facilitated by a removal of regulatory hurdles and payment parity, at least temporarily. At the same time, however, many patients still need to return to the clinic for routine infusions of anti-cancer therapy that obviate much of the value of remote clinic visits, and many patients remain limited by access to hardware, fast and reliable internet, and technical expertise. While we need to address these shortcomings and ensure training of health care professionals in "webside manner" with patients, as well as to work to develop ways to incorporate remote care in the conduct of clinical trials, telemedicine is poised to emerge not merely as an interim solution to a transient challenge but as a valuable tool ideally suited to deliver cancer care efficiently for a subset of patients well suited to adopt this platform.

Non-small cell lung cancer with very limited extent of metastatic spread commonly is termed, oligometastatic disease (OMD), and typically described as no more than 3 to 5 lesions. Definitive local therapy potentially leads to significant improvement in progression-free survival and overall survival. OMD may occur de novo prior to initiation of systemic therapy or as an induced state after initiation of systemic therapy. Although prospective data are limited to small trials, they have consistently supported local therapy as an appropriate consideration if not a clear standard of care for well-selected patients. Several trials in OMD are ongoing.

Background We evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non–small-cell lung cancer. Patients and Methods Patients with treatment-naive squamous non–small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m2 on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS). Results Overall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator’s discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in ≥ 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC). Conclusions The results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.

Purpose Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib. Methods This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR). Results Sixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3–16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3–27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa. Conclusions Despite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib. Electronic supplementary material The online version of this article (doi:10.1007/s00280-017-3283-z) contains supplementary material, which is available to authorized users.

This study assesses differences in survival according to the time interval between non–small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy.

Purpose The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) guideline on molecular testing for the selection of patients with lung cancer for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors was considered for endorsement. Methods American Society of Clinical Oncology (ASCO) staff reviewed the CAP/IASLC/AMP guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and present options that will be acceptable to patients. The CAP/IASLC/AMP guideline comprises 37 recommendations (evidence grade A or B), expert consensus opinions, or suggestions that address the following five principal questions: (1) When should molecular testing be performed? (2) How should EGFR testing be performed? (3) How should ALK testing be performed? (4) Should other genes be routinely tested in lung adenocarcinoma? (5) How should molecular testing be implemented and operationalized? Conclusion The ASCO review panel endorses the CAP/IASLC/AMP guideline. This guideline represents an important advance toward standardization of EGFR and ALK testing practices and is of major clinical relevance in advancing the care of patients with lung cancer. In the Discussion section, the ASCO review panel highlights three evolving areas: advances in ALK testing methodology, considerations for selecting appropriate populations for molecular testing, and emergence of other targetable molecular alterations.

Lung cancer is the leading cause of cancer-related death in the United States. Outcomes for patients with lung cancer have reached a plateau with cytotoxic chemotherapy. Lung cancer remains very much at the vanguard of the new revolution in cancer therapy using molecular targets. Although striking improvements in survival have been observed in the treatment of chronic myeloid leukemia, gastrointestinal stromal tumors, and in a subset of breast cancer using this approach, the impact of targeted therapies in lung cancer is quite modest. Along with advances in imaging and cancer genomics, there is now considerable optimism that the pace of progress in the treatment of lung cancer will accelerate in the next 10 years. As has been the custom for the past 8 years, leading experts in the biology, diagnosis and treatment of lung cancer met for three days to discuss current areas of research and future directions. This summary provides a brief snapshot of the discussions held at the 8th Annual Meeting on Targeted Therapies for Lung Cancer sponsored by the International Association for the Study of Lung Cancer in Santa Monica in early February 2008.

TPS9101 Background: Platinum-based chemotherapy (chemo) is the current standard of care for patients (pts) with newly diagnosed advanced non-squamous NSCLC. The combination of platinum-based chemo and pemetrexed (pem) provides comparable benefit to pts as other standard platinum doublets commonly used and has a favorable toxicity profile. However, the survival benefit conferred by this combination leaves considerable room for improvement. The anti–PD-L1 mAb atezolizumab (atezo) inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. In the OAK trial, pts with 2L/3L advanced NSCLC had improved mOS in the atezo arm (13.8 mo) vs the docetaxel arm (9.6 mo), with a survival benefit observed across PD-L1 expression levels. The potential for chemo to further augment responses to atezo, with tolerable safety, has also been demonstrated. A global, Phase III, randomized, open-label trial, IMpower132 (NCT02657434), is being conducted to evaluate 1L atezo + platinum-based chemo + pem in chemo-naive pts with stage IV NSCLC. Methods: Eligibility criteria include stage IV NSCLC, measurable disease (RECIST v1.1), no prior chemo and ECOG PS 0-1. Exclusion criteria include tumors known to harbor EGFR or ALK driver mutations, untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Pts will be enrolled regardless of PD-L1 expression status and randomized to the treatment arms. Pts will be stratified by sex, ECOG PS, type of chemo (carboplatin [carbo] vs cisplatin [cis]) and smoking status. Pts will receive four or six 21-day cycles of either atezo + carbo/cis + pem or carbo/cis + pem. Following the induction phase, pts will receive maintenance atezo + pem or pem alone, depending on their allocated treatment regimen. Pts receiving atezo may continue until loss of clinical benefit.Co-primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include IRF-assessed PFS, investigator-assessed ORR and safety. Predictive biomarkers associated with efficacy will be evaluated. Approximately 568 pts will be enrolled. Clinical trial information: NCT02657434.

e20503 Background: Most ALK+ NSCLC patients (pts) receiving CRZ eventually experience disease progression. Based on promising activity in a phase 1/2 trial, a randomized phase 2 trial of the ALK inhibitor BRG in pts with CRZ-refractory, advanced ALK+ NSCLC (ALTA; NCT02094573) was initiated. Responses and adverse events (AEs) varied with starting dose; therefore, ALTA was designed to evaluate 2 distinct BRG regimens. Methods: Pts were stratified by presence of baseline (BL) brain metastases and best response to prior CRZ and randomized 1:1 to receive BRG at 90 mg qd (arm A) or 180 mg qd with a 7-d lead-in at 90 mg (arm B). Primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1. Results: In 222 pts (arm A/B, n=112/n=110), median age was 51/57 y; 71%/67% had brain metastases. As of May 31, 2016, 51%/56% (A/B) continued to receive BRG; median follow-up was 10.2/11.0 mo. Table shows efficacy. In pts with measurable BL brain metastases (A/B, n=26/n=18), confirmed intracranial ORR was 46%/67%. Most common treatment-emergent AEs (A/B) were: nausea 36%/43%, diarrhea 21%/39%, cough 23%/36%, headache 28%/30%, vomiting 28%/26%; grade ≥3 AEs included increased CPK 3%/10%, hypertension 6%/6%, pneumonia 3%/5%, increased lipase 5%/3%. A subset of pulmonary AEs with early onset (median: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); 7/14 pts were successfully retreated. Dose reductions (8%/23%, A/B) and discontinuations (3%/10%) due to AEs were reported. Conclusions: BRG showed substantial activity, robust PFS, and acceptable safety at both dose levels, with numerically improved efficacy (particularly PFS and intracranial ORR) at 180 mg (with lead-in). Clinical trial information: NCT02094573. [Table: see text]

9007Background: We report the first results of a pivotal ph 2 trial of BRG in pts with ALK+ NSCLC. BRG, an investigational oral tyrosine kinase inhibitor (TKI) with preclinical activity against rea...

63 Background: The correlation of radiological response and pt-reported outcomes (PROs) in advanced NSCLC remains underreported. This interim analysis evaluated QoL by response (RECIST v1.1) in SCC NSCLC pts treated with nab-P/C during the induction part of the ABOUND.sqm study. Methods: In the ongoing phase III ABOUND.sqm study, pts with advanced SCC NSCLC are treated with first-line nab-P 100 mg/m2 d 1, 8, 15 and C AUC 6 mg•min/mL d 1 (21-d cycles) for 4 cycles (induction). Pts not progressing are randomized 2:1 to maintenance nab-P 100 mg/m2d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until progression. The primary endpoint is PFS from randomization to maintenance. QoL, an exploratory endpoint, was assessed with predefined PRO instruments, LCSS and EQ-5D-5L, on d 1 of each cycle. Pts with a radiological CR/ PR are considered responders (R) in this analysis (57% of evaluable pts). As the study is ongoing, this pre-planned analysis included QoL and tumor response data that were reported up to the cutoff date. Results: Baseline (BL) characteristics were similar for Rs (n = 73) and non-Rs (n = 55). Over 80% of pts completed BL + ≥ 1 post-BL PRO assessments. For LCSS, average total score and symptom burden index improved during induction chemotherapy; a higher percentage of Rs vs non-Rs had clinically meaningful improvements (≥ 10 mm [VAS]) from BL in composite LCSS cough, shortness of breath, & hemoptysis (56% vs 38%). Of pts reporting BL EQ-5D-5L dimension problem(s), a higher percentage of Rs vs non-Rs reported complete resolution at least once during treatment (Table). Conclusions: These results indicate that Rs and non-Rs maintained/improved QoL during induction therapy with nab-P/C. Rs appeared to have greater improvements in LCSS and EQ-5D-5L. Radiological response translates into meaningful QoL improvement. Clinical trial information: NCT02027428. [Table: see text]

It has been quite challenging to demonstrate significant improvements in survival for patients with non-small-cell lung cancer (NSCLC) over the past decade, but targeted therapies such as epidermal growth factor receptor (EGFR) inhibitors and angiogenesis inhibitors have been associated with benefits sufficient to alter our treatment standards. In addition to variations within these classes and combinations of such agents, several novel targeted therapy strategies have been introduced and are now emerging with encouraging results in early clinical trials for patients with advanced NSCLC. Immunotherapies targeting the MUC1 protein, MAGE-A3, and EGFR have shown early evidence of clinical benefits. Belagenpumatucel-L is a nonspecific allogeneic vaccine derived from multiple lung cancer cell lines, and the agent talactoferrin alfa might improve clinical outcomes based on broad immune system activation and stimulation. Other approaches that inhibit insulin-like growth factor receptor or heat-shock protein, both involved with multiple pathways involved with cell growth and survival, have shown activity in early trials and are moving forward in trials that specifically focus on patients with advanced NSCLC. This article reviews current data and future directions for each of these approaches.

8009 Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global ...

8019 Background: Crizotinib is an approved treatment for patients (pts) with ALK-rearranged (ALK+) NSCLC. However, progression on crizotinib, particularly in the CNS, frequently occurs within a yea...

7517 Background: Despite recent changes to lung adenoCa pathologic classification, adv stage BAC remains a definable and clinically applicable entity. Patients (pts) with BAC, as well as never-smoking (NS) pts with adv lung adenoCa, have emerged as relevant clinical subpopulations with a high probability of clinical benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), likely related to the high proportion of activating mutations in the EGFR gene in such pts. Based on these results and the potential for increased clinical activity conferred by addition of B to E, SWOG initiated a pair of phase II trials of this combination in pts with adv BAC (S0635) or NS pts with adv lung adenoCa (S0636). Methods: NS pts with BAC or adenoBAC were preferentially enrolled on S0636. A total of 78 and 85 eligible pts were enrolled and treated on the S0635 and S0636 trials, respectively. Patients received E 150 mg PO daily and B 15 mg/kg IV q21 days until progression or prohibitive toxicity. Tumor tissue submission for pathologic review and assessment of molecular markers was mandated. Results: Pt demographics of the two trials are as shown in the table below. RECIST response rate among 61 BAC pts on S0635 with measurable disease was 18%, and among 53 NS pts on S0636, it was 47%. Median progression-free survival is 5 and 8 months (mo) on S0635 and S0636, respectively; median overall survival (OS) is 17 and 26 mo on S0635 and S0636, respectively. Toxicity consisted primarily of rash, diarrhea, and hypertension; no treatment-related deaths were reported. Molecular marker studies will be presented separately. Conclusions: In populations selected by clinical parameters, E withB is associated with modest toxicity and encouraging clinical efficacy that exceeded the prespecified OS threshold of 16 mo in studies of both adv BAC and NS pts, exceeding two years in NS pts. [Table: see text]

7552 Background: S0636 investigated the combination of erlotinib and bevacizumab in never-smoking NSCLC patients with confirmed adenocarcinoma histology (H. West ASCO 2011). Patient eligibility was not restricted by molecular selection. Median PFS and OS were encouraging at 8 and 26 months. An analysis of molecular markers was undertaken, focusing initially on the EGFR pathway. Methods: EGFR analysis included gene copy number, mutation and protein expression. Copy number was conducted by FISH using the Colorado scoring system. An immunohistochemistry H score was developed for EGFR protein expression analysis, ranging from 0 to 400. Specimens were evaluable from 42 of the 85 eligible patients. Results: FISH positivity was identified in 17/35 pts (49%), 11 with high polysomy and 6 with true gene amplification. EGFR activating mutations were seen in 10/33 pts (30%). IHC H-score >200 was observed in 17/40 pts (43%). All EGFR markers were significantly correlated with one another. In the EGFR WT subgroup, FISH-positive patients outperformed FISH-negative pts (mPFS 20 vs, 6 months, p=0.06). Conclusions: Careful analysis of EGFR markers (mutation, FISH and IHC) identified S0636 patients with favorable PFS and encouraging trends for OS. EGFR FISH and IHC provided additional predictive information beyond that of EGFR mutation status. Supported in part by DHHS: CA32102 and CA38926, and in part by Genentech. [Table: see text]

7030 Background: BAC subtypes are increasing in incidence, particularly in younger, never-smoking women. Studies with EGFR inhibitors have demonstrated response rates of 20–30% in patients (pts) with advanced BAC. However, no methods have been established to select pts for such treatments. Methods: In this study EGFR copy number by fluorescence in situ hybridization (FISH) was assessed and correlated to treatment response and survival. Tumor tissue from 81 pts with advanced stage BAC treated with gefitinib 500mg/day in the SWOG protocol S0126 were analyzed by FISH and classified in two main categories: FISH positive (high polysomy/gene amplification) and FISH negative (disomy, trisomy and low polysomy). Results: Fifty-five pts with measurable disease were evaluated for response using the RECIST criteria. Among 19 FISH positive pts, 12 (63%) had disease control (response or stable disease) versus 14/36 pts (39%) in the FISH negative group (exact p-value=0.099). Eighty-one pts were evaluable for survival, a...

9587 Background: In the global phase III IMpower150 study (NCT02366143), atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP] (ABCP) showed significant improvements in PFS and OS vs BCP in patients with chemotherapy-naive metastatic NSCLC (Socinski et al. N Engl J Med 2018). Because bev has been shown to delay or prevent brain metastases progression in NSCLC (Fu et al. J Chemother 2016; Ilhan-Mutlu et al. Mol Can Ther 2016), exploratory analyses were conducted to assess the development of brain metastases in patients treated with ABCP, BCP and atezo + CP (ACP) in IMpower150. Methods: A total of 1202 patients (intention-to-treat [ITT] population) were randomized 1:1:1 to receive ABCP, ACP or BCP. Doses were given every 3 weeks: atezo 1200 mg, bev 15 mg/kg, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m2. Co-primary endpoints were investigator-assessed PFS and OS in ITT–wild-type (no EGFR or ALK alterations) patients. Exploratory analyses included the rate and time to development (TTD) of new brain metastases in the ITT population, regardless of the presence of baseline brain metastases, as well as safety. Brain scans were performed as clinically indicated, and analyses were based on investigator assessments. Results: With a minimum follow-up of 32.4 months in the ITT population (data cutoff: September 13, 2019), 100 patients had developed brain metastases, with the highest rate of new brain lesions seen in the ACP (11.9%) vs the ABCP (7.0%) and BCP (6.0%) arms (table). Median TTD was not reached in any arm; a trend toward delayed TTD was seen in the ABCP vs BCP arm (HR, 0.68 [95% CI: 0.39, 1.19]). Among patients with and without brain metastases, 17 (35.4%) and 155 (44.0%) in the ACP arm, 18 (64.3%) and 207 (56.7%) in the ABCP arm and 10 (41.7%) and 183 (49.5%) in the BCP arm had Grade 3-4 treatment-related adverse events, respectively. Conclusions: The ACP arm had the highest rate of new brain lesions, whereas the ABCP and BCP arms had similar, lower rates. Taken together with the trend toward delayed development of new brain lesions with ABCP, the data suggest that adding atezo to BCP may not reduce the rate of new brain lesion development but may delay the time to new lesion development. No new safety signals were observed in this exploratory analysis. Clinical trial information: NCT02366143 . [Table: see text]