MYCN drives chemoresistance in small cell lung cancer while USP7 inhibition can restore chemosensitivity.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer characterized by initial chemosensitivity followed by emergence of chemoresistant disease. To study roles for MYCN amplification in SCLC progression and chemoresistance, we developed a genetically engineered mouse model of MYCN-overexpressing SCLC. In treatment-naïve mice, MYCN overexpression promoted cell cycle progression, suppressed infiltration of cytotoxic T cells, and accelerated SCLC. MYCN overexpression also suppressed response to cisplatin-etoposide chemotherapy, with similar findings made upon MYCL overexpression. We extended these data to genetically perturb chemosensitive patient-derived xenograft (PDX) models of SCLC. In chemosensitive PDX models, overexpression of either MYCN or MYCL also conferred a switch to chemoresistance. To identify therapeutic strategies for MYCN-overexpressing SCLC, we performed a genome-scale CRISPR-Cas9 sgRNA screen. We identified the deubiquitinase USP7 as a MYCN-associated synthetic vulnerability. Pharmacological inhibition of USP7 resensitized chemoresistant MYCN-overexpressing PDX models to chemotherapy in vivo. Our findings show that MYCN overexpression drives SCLC chemoresistance and provide a therapeutic strategy to restore chemosensitivity.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors.

Purpose and Methods Trop-2 is a glycoprotein over-expressed in many solid tumors but at low levels in normal human tissue, providing a potential therapeutic target. We conducted a phase 1 dose-finding study of PF-06664178, an antibody-drug conjugate that targets Trop-2 for the selective delivery of the cytotoxic payload Aur0101. The primary objective was to determine the maximum tolerated dose and recommended phase 2 dose. Secondary objectives included further characterization of the safety profile, pharmacokinetics and antitumor activity. Eligible patients were enrolled and received multiple escalating doses of PF-06664178 in an open-label and unblinded manner based on a modified continual reassessment method. Results Thirty-one patients with advanced or metastatic solid tumors were treated with escalating doses of PF-06664178 given intravenously every 21 days. Doses explored ranged from 0.15 mg/kg to 4.8 mg/kg. Seven patients experienced at least one dose limiting toxicity (DLT), either neutropenia or rash. Doses of 3.60 mg/kg, 4.2 mg/kg and 4.8 mg/kg were considered intolerable due to DLTs in skin rash, mucosa and neutropenia. Best overall response was stable disease in 11 patients (37.9%). None of the patients had a partial or complete response. Systemic exposure of PF-06664178 increased in a dose-related manner. Serum concentrations of free Aur0101 were substantially lower than those of PF-06664178 and total antibody. No correlation of Trop-2 expression and objective response was observed, although Trop-2 overexpression was not required for study entry. The intermediate dose of 2.4 mg/kg appeared to be the highest tolerated dose, but this was not fully explored as the study was terminated early due to excess toxicity. Conclusion PF-06664178 showed toxicity at high dose levels with modest antitumor activity. Neutropenia, skin rash and mucosal inflammation were dose limiting toxicities. Findings from this study may potentially aid in future antibody drug conjugate design and trials.

Detection of HPV in oral rinse samples from OPSCC and non-OPSCC patients.

BACKGROUND: Due to the increasing rates of oropharyngeal cancer, oral HPV infection is a significant concern. Methods for detecting oral HPVs is not standardized as there are different techniques available. We propose that use of oral rinse samples to detect for HPVs is a suitable technique within a clinic setting. Thus, our main objective is to study HPV detection in oral rinse samples. METHODS: In our study, we used oral rinse sample collection coupled with real-time PCR to detect for HPVs types 16 and 18, and preferentially amplified FAP PCR samples to detect for a broad range of HPVs, in oropharyngeal squamous cell carcinoma (OPSCC), non-OPSCC, and healthy patients. RESULTS: Thirty three percent of 100 cancer patients were positive for any type of HPV; of those 23 were positive for HPV16. Only 1 of 110 healthy controls was positive (this subject was positive for HPV18). CONCLUSION: Our results indicate that HPV detection in oral rinse samples may be useful as a screening tool to detect HPV-associated oral cancers.

Occult primary, version 3.2014.

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation.

Central Line Patency: Management With Normal Saline Flushes for Adult Patients With Cancer.

BACKGROUND: Central venous catheter (CVC) maintenance is critical in administering chemotherapy, transfusions, and high-frequency laboratory draws. Although normal saline (NS) flushes have been associated with similar incidences of irreversible port occlusions as heparin among adult patients with cancer and ports, additional research is needed regarding NS efficacy in other central line maintenance within large populations with cancer. OBJECTIVES: The aim of this study was to analyze changes in reported CVC line patency via tissue plasminogen activator (tPA) administration rates in ports and other central lines because of an institutional switch from heparin to NS as preferred flushes in adult ambulatory patients with cancer. METHODS: Retrospective data were collected from patients with ports (3,706 prepolicy, 3,402 postpolicy) and nonport CVCs (816 prepolicy, 694 postpolicy). FINDINGS: Patients with nonport CVCs experienced similar tPA usage pre- versus postpolicy, versus an increased rate of tPA usage for ports. This policy resulted in institutional savings of $28,695.92. NS flushes are as effective as heparin for maintaining patency in ports and other CVCs for adult outpatients with cancer and address safety concerns with heparin-associated complications.

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study.

BACKGROUND: Histone deacetylase (HDAC) inhibitors have potential to augment the effectiveness of immune checkpoint inhibitors and overcome treatment resistance. This dose-escalation/expansion study (NCT02805660) investigated mocetinostat (class I/IV HDAC inhibitor) plus durvalumab in patients with advanced non-small cell lung cancer (NSCLC) across cohorts defined by tumor programmed death-ligand 1 (PD-L1) expression and prior experience with anti-programmed cell death protein-1 (anti-PD-1) or anti-PD-L1 regimens. PATIENTS AND METHODS: Sequential cohorts of patients with solid tumors received mocetinostat (starting dose: 50 mg TIW) plus durvalumab at a standard dose (1500 mg Q4W) to determine the recommended phase II dose (RP2D: phase I primary endpoint), based on the observed safety profile. RP2D was administered to patients with advanced NSCLC across 4 cohorts grouped by tumor PD-L1 expression (none or low/high) and prior experience with anti-PD-L1 /anti-PD-1 agents (naïve, clinical benefit: yes/no). The phase II primary endpoint was objective response rate (ORR, RECIST v1.1). RESULTS: Eighty-three patients were enrolled (phase I [n = 20], phase II [n = 63]). RP2D was mocetinostat 70 mg TIW plus durvalumab. ORR was 11.5% across the phase II cohorts, and responses were durable (median 329 days). Clinical activity was observed in NSCLC patients with disease refractory to prior checkpoint inhibitor treatment: ORR 23.1%. Across all patients, fatigue (41%), nausea (40%), and diarrhea (31%) were the most frequent treatment-related adverse events. CONCLUSION: Mocetinostat 70 mg TIW plus durvalumab at the standard dose was generally well tolerated. Clinical activity was observed in patients with NSCLC unresponsive to prior anti-PD-(L)1 therapy.

A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer.

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. RESULTS: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. CONCLUSIONS: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01011075.

A 66-year-old woman with newly diagnosed oligometastatic non-small cell lung cancer.

A 66-year-old woman presented with newly diagnosed stage IV non-small cell lung cancer (NSCLC) and a large adrenal metastasis. She initially had flu-like symptoms and dyspnea and was found to have a right upper lobe (RUL) lung nodule. Chest CT showed a 1.4-cm spiculated RUL lung nodule, peripheral right lung nodule, right perihilar mass, and 10.9-cm left adrenal mass. PET/CT showed enhancement of the RUL nodule, hilar mass, and left adrenal mass. She presented for evaluation of treatment options. This case was thought to represent an instance of oligometastatic stage IV NSCLC. Literature suggests that a select patient population with otherwise resectable disease may benefit from surgical resection of a lung primary and the isolated metastasis with improved survival. This seems to be most effective in patients who have undergone a complete staging evaluation with PET scan; CT of the chest, abdomen, and pelvis; and a brain MRI revealing T1-2, N0-1, M-oligo disease. This radical approach should be reserved for patients with potentially curative disease based on the staging evaluation and who are otherwise good surgical candidates.

Development of Neuropathic Arthropathy With Entrectinib: Case Report.

TRK inhibition can lead to on-target neurologic adverse events. Two cases illustrate the development of neuropathic arthropathy as a side effect of entrectinib. After starting entrectinib, both patients developed foot pain, swelling, and sensory changes with magnetic resonance imaging revealing marrow edema. Providers should have a low threshold to investigate foot pain or gait abnormalities thoroughly with magnetic resonance imaging and referral to specialists to aid in the diagnosis of neuropathic arthropathy, with consideration to transition to an alternative agent.

Impact of Diagnostic Delays on Lung Cancer Survival Outcomes: A Population Study of the US SEER-Medicare Database.

PURPOSE: Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. METHODS: We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). RESULTS: In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. CONCLUSION: Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

BACKGROUND: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. METHODS: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. RESULTS: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05-5.71). There was no significant association between toxicity and any patient characteristic. CONCLUSIONS: We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

Prognostic Value of Early Fluorodeoxyglucose-Positron Emission Tomography Response Imaging and Peripheral Immunologic Biomarkers: Substudy of a Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer.

Purpose: We sought to examine the prognostic value of fluorodeoxyglucose-positron emission tomography (PET) imaging during chemoradiation for unresectable non-small cell lung cancer for survival and hypothesized that tumor PET response is correlated with peripheral T-cell function. Methods and Materials: Forty-five patients with American Joint Committee on Cancer version 7 stage IIB-IIIB non-small cell lung cancer enrolled in a phase II trial and received platinum-doublet chemotherapy concurrent with 6 weeks of radiation (NCT02773238). Fluorodeoxyglucose-PET was performed before treatment start and after 24 Gy of radiation (week 3). PET response status was prospectively defined by multifactorial radiologic interpretation. PET responders received 60 Gy in 30 fractions, while nonresponders received concomitant boosts to 74 Gy in 30 fractions. Peripheral blood was drawn synchronously with PET imaging, from which germline DNA sequencing, T-cell receptor sequencing, and plasma cytokine analysis were performed. Results: Median follow-up was 18.8 months, 1-year overall survival (OS) 82%, 1-year progression-free survival 53%, and 1-year locoregional control 88%. Higher midtreatment PET total lesion glycolysis was detrimental to OS (1 year 87% vs 63%, P < .001), progression-free survival (1 year 60% vs 26%, P = .044), and locoregional control (1 year 94% vs 65%, P = .012), even after adjustment for clinical/treatment factors. Twenty-nine of 45 patients (64%) were classified as PET responders based on a priori definition. Higher tumor programmed death-ligand 1 expression was correlated with response on PET (P = .017). Higher T-cell receptor richness and clone distribution slope were associated with improved OS (P = .018-0.035); clone distribution slope was correlated with PET response (P = .031). Conclusions: Midchemoradiation PET imaging is prognostic for survival; PET response may be linked to tumor and peripheral T-cell biomarkers.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

NCCN Clinical Practice Guidelines Occult primary.

Occult primary tumors, or cancers of unknown primary (CUPs), are defined as histologically proven metastatic malignant tumors whose primary site cannot be identified during pretreatment evaluation. They have a wide variety of clinical presentations and a poor prognosis in most patients. Patients with occult primary tumors often present with general complaints, such as anorexia and weight loss. Clinical absence of primary tumor, early dissemination, aggressiveness, and unpredictability of metastatic pattern are characteristic of these tumors. Life expectancy is very short, with a median survival of 6 to 9 months. In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy is only palliative and does not significantly improve long-term survival. However, certain clinical presentations of these tumors are associated with a better prognosis. Special pathologic studies can identify subsets of patients with tumor types that are more responsive to chemotherapy. Treatment options should be individualized for this selected group of patients to achieve improved response and survival rates.

A Phase II study of nab-Paclitaxel (nab-P) in patients with advanced non-small cell lung cancer with EGFR mutations after frontline tyrosine kinase inhibitor therapy.

BACKGROUND: Patients with metastatic non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation have effective targeted therapy options initially but most patients eventually progress and receive cytotoxic chemotherapy. In this single-institution phase II study, we evaluated the role of nab-paclitaxel monotherapy in this patient population. PATIENTS AND METHODS: Patients with metastatic NSCLC with an activating EGFR mutation whose disease progressed after frontline tyrosine kinase inhibitor therapy and who were chemotherapy naïve received nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint was response rate per RECIST 1.1 and secondary endpoints were duration of response, progression free survival, toxicity and overall survival. RESULTS: A total of 27 patients were enrolled and 21 patients were evaluable for response. Median age was 65 (range 52-81), 69% of patients were women, 42% of patients did not having a smoking history. 31% of patients had central nervous system (CNS) metastatic disease at baseline. Confirmed partial response was documented in 9 of 26 patients (35%, 95% CI 17-56) and disease control rate was 58% (95% CI 35-73). CNS was a common first site of progression. Median progression free survival was 4.0 months (95% CI 1.8-5.2). No new safety signals were observed. CONCLUSION: Single agent nab-paclitaxel showed modest antitumor activity in patients with EGFR mutation positive NSCLC and may be an option in patients who are platinum ineligible. Patients often progressed in the CNS and the results underscores the importance of CNS activity of systemic therapies in this patient population.

Impact of Clinical Trial Participation on Survival of Patients with Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION: The impact of clinical trial participation on overall survival is unclear. We hypothesized that enrollment in a therapeutic drug clinical trial is associated with longer overall survival in patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We linked electronic medical record and Washington State cancer registry data to identify patients with metastatic NSCLC diagnosed between January 1, 2007, and December 31, 2015 who received treatment at a National Cancer Institute-designated cancer center. The exposure was trial enrollment. The primary outcome was overall survival, defined as the date of second-line treatment initiation to date of death or last follow-up. We used a conditional landmark analysis starting at the date of second-line treatment initiation and propensity scores with inverse probability of treatment weighting to estimate the association between trial enrollment and survival. RESULTS: Of 215 patients, 40 (19%) participated in a second-line trial. Trial participants were more likely to be never smokers (45% vs 27%), have a good performance status (88% vs 77%) and have EGFR (48% vs 14%) and ALK mutations (8% vs 5%) than nonparticipants. Trial participants had similar overall survival to nonparticipants (HR 1.05; 95% CI, 0.72, 1.53; p = 0.81) after adjusting for sociodemographic and disease characteristics. CONCLUSION: Accounting for the immortal time bias and selection bias, trial participation does not appear detrimental to survival. This finding may be reassuring to patients and supports programs and policies to improve clinical trial access.

Adaptive Fluorodeoxyglucose-Positron Emission Tomography Based Chemotherapy Selection for Metastatic Non-small Cell Lung Cancer.

Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naïve patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results  Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen.