Advanced Squamous Cell Lung Cancer Research Articles

1567P - Efficacy of weekly paclitaxel-bevacizumab combination in advanced non squamous non-small cell lung cancer (NSCLC): A retrospective multicentric study

BackgroundULTIMATE, a phase III trial, showed a significant superiority in terms of progression free survival (PFS) and less toxicity of the combination paclitaxel-bevacizumab versus docetaxel as second or third-line treatment. With the growing role of immunotherapy as first-line setting for advanced non-small cell lung cancer (NSCLC), there is a need to redefine strategies to failure. The use of the paclitaxel-bevacizumab combination could be an option. MethodsThis retrospective study identified patients treated with paclitaxel and bevacizumab according to the ULTIMATE study in 3 centers in France. Main objectives were to describe safety and efficacy of this combination in metastatic non-squamous NSCLC as second-line therapy or beyond, with a particular interest for the sub-group of patients treated just after immune checkpoint inhibitors. ResultsFrom 1st September 2010 to 1st avril 2018, 76 patients started the paclitaxel-bevacizumab combination : 42 (55%) male, 18 (24%) and 36 (47%) treated in second and third-line respectively, and 22 (29%) in fourth-line or more. Objective response rate (ORR) was 37% (28/76) and disease control rate 74 % (56/76). Median PFS and OS were 5,7 [95%CI: 4,1-6,9] months and 11,2 [95%CI: 8-not reached] months respectively. For patients treated in second and third-line, ORR was respectively 39% and 42%, PFS 4 months [95%CI: 2,5-7,7] and 6 months [95%CI: 4-7], OS 9,4 months [95%CI: 2,7-not reached] and was not reached in third-line at 12 months. Grade 3–4 adverse events included asthenia 5% (4/76), neurotoxicity 3% (2/76), bleeding events 4% (3/76), and hematological toxicity 1% (1/76). Interestingly, in the subgroup of patients treated with immunotherapy just before paclitaxel-bevacizumab (33/76), ORR was 42% (14/33), median PFS was 6,2 [95% CI: 4,6-7,7] months, and median overall survival was not reached at 12 months. ConclusionsThis results exhibited an acceptable toxicity profile and an encouraging efficacy as second-line treatment or beyond for non-squamous NSCLC patients. For patient treated just after immunotherapy the results are very promising. Legal entity responsible for the studyDr Chantal Decroisette CH Annecy Genevois France. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Exploratory analysis of JFCM: Predictive value of rash, EGFR expression, and EGFR copy for necitumumab in squamous NSCLC

Abstract Background JFCM, an open-label, multicenter, phase 1b/2 study (n = 181), demonstrated that addition of necitumumab (N) to gemcitabine and cisplatin (GC) resulted in significant improvement in overall survival (OS; hazard ratio [HR] = 0.66) in the first-line treatment of advanced squamous non-small cell lung cancer (NSCLC) patients in Japan. Previous studies have suggested that rash, EGFR expression, and EGFR copy number gain might be associated with the efficacy of EGFR-targeting drugs in the treatment of squamous NSCLC. Methods Our analysis assessed: development of acne-like rash in the first cycle; EGFR expression (evaluated by H-score of immunohistochemistry, H ≥ 200 vs H Results Of the 90 patients in the GC+N arm, 80 (88.9%) had first-cycle rash. Median OS was 14.52 vs 15.93 months (HR = 1.39) in patients experiencing first-cycle rash vs those without rash in the GC+N arm. For EGFR expression, the majority of patients had H Conclusion Our analysis did not identify first-cycle rash, EGFR expression, and EGFR copy number gain as predictive markers of survival in JFCM study. (Trial Registration Number: NCT01763788)

Population PK/PD Analysis of Necitumumab: Dose justification for Squamous Cell Lung Cancer (SqCLC) Patients in Japan

Abstract Background Necitumumab (NEC) in combination with gemcitabine+cisplatin (GC) demonstrated significant improvement in overall survival (OS) compared to GC in advanced SqCLC patients (pts) in Global Ph3 study JFCC. In Study JFCM Ph2 part, NEC in combination with GC improved OS compared to GC in SqCLC pts in Japan. Population PK/PD analysis including Study JFCM was conducted to determine the adequacy of the dose in pts in Japan based on NEC PK, and relationship between exposure and efficacy and safety. Methods Two studies, one of which Study JFCM, were added into the analysis previously performed with five Ph 1, 2, and 3 studies. The effect of Japan/non-Japan origin on NEC PK was assessed. Simulations were performed to compare predicted NEC serum concentrations after flat 800 mg and body weight based dosing. The relationship between exposure and OS in Studies JFCC and JFCM Ph2 part was explored. The relationship between exposure and safety measurements (hypomagnesemia, rash and thromboembolic events) in Studies JFCC and JFCM Ph2 part was explored. Results Population PK analysis included blood samples collected from 967 pts (including 114 pts in Japan) treated with NEC. PK parameters were similar between Japanese and non-Japanese pts. NEC PK is dependent on body weight; however, simulations indicated weight-based dosing would not significantly decrease PK variability. Exposure-response analysis included 1195 pts, including 181 pts in Japan. Exposure-efficacy analysis suggested that pts with higher NEC concentration had longer OS, however, majority of pts in both studies had steady state exposure greater than EC80. No correlation was observed between NEC serum exposure and severity of hypomagnesemia or rash. No correlation was observed between NEC serum exposure and risk of treatment emergent thromboembolic events. Conclusion Population PK/PD analysis supports the administration of 800 mg NEC on Day 1 and 8 of a 21-day cycle as an appropriate dose in SqCLC pts in Japan.

Phase II study of nedaplatin and amrubicin as first‐line treatment for advanced squamous cell lung cancer

BackgroundThe first‐line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment‐naïve patients with advanced SCC.MethodsA total of 21 treatment‐naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2) on day 1 and amrubicin (25 mg/m2) on days 1–3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression‐free survival (PFS), and drug toxicities.ResultsPartial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5–52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment‐related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed.ConclusionThe efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment‐naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.

A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer

PurposeThis study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity.Patients and methodsThis open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m2) administered intravenously on a every 3-week schedule. Adverse event (AE) rates and tumour responses were determined. Heregulin messenger RNA (mRNA) and HER3 protein expression were investigated in archival tumour biopsies.ResultsAltogether, 12 patients received lumretuzumab in combination with carboplatin and paclitaxel. The most frequent AEs were gastrointestinal, haematological and nervous system toxicities, which were generally mild and manageable. Partial responses were observed in 3 of 12 patients lasting 81, 177 and 207 days. All responses were achieved in tumours expressing higher heregulin mRNA levels.ConclusionLumretuzumab in combination with carboplatin and paclitaxel was well tolerated. Objective responses were enriched in tumours expressing higher heregulin mRNA levels.

Effectiveness of first-line treatments in metastatic squamous non-small-cell lung cancer.

Commonly used first-line (1L) chemotherapies for patients with advanced squamous-cell lung cancer (scc) include gemcitabine-platinum (gp), nab-paclitaxel-carboplatin (nabpc), and sb-paclitaxel-carboplatin (sbpc) regimens. However, no head-to-head trials have compared those treatments. In the present study, we compared the efficacy of 1L gp, nabpc, and sbpc in patients with scc and in patients with scc who subsequently received second-line (2L) immunotherapy. Medical records of patients who initiated the 1L treatments of interest between June 2014 and October 2015 were reviewed by 132 participating physicians. Kaplan-Meier curves were used to evaluate overall survival (os), progression-free survival (pfs), and treatment discontinuation (td), and then Cox proportional hazards regression was used to compare the results between the cohorts. Medical records of 458 patients with scc receiving gp (n = 139), nabpc (n = 159), or sbpc (n = 160) as 1L therapy were reviewed. Median os was longer with nabpc (23.9 months) than with gp (16.9 months; adjusted hazard ratio vs. nabpc: 1.55; p < 0.05) and with sbpc (18.3 months; adjusted hazard ratio: 1.42; p = 0.10). No differences were observed in pfs (median pfs: 8.8, 8.0, and 7.6 months for gp, nabpc, and sbpc respectively; log-rank p = 0.76) or in td (median td: 5.5, 5.7, and 4.6 months respectively; p = 0.65). For patients who subsequently received 2L immunotherapy, no differences in os were observed (median os: 27.3, 25.0, and 23.0 months respectively; p = 0.59). In a nationwide sample of scc patients, longer median os was associated with 1L nabpc than with gp and sbpc. Median os for all 1L agents considered was similar in the subgroup of patients who sequenced to a 2L immunotherapy.

A phase II study of talazoparib (BMN 673) in patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer (Lung-MAP Sub-Study, S1400G).

9022 Background: This signal finding study was designed to evaluate the clinical efficacy of a PARP inhibitor, talazoparib, in advanced stage squamous cell lung cancer harboring HRRD. Methods: Eligible patients (pts) identified through the parent S1400 screening platform were required to have a deleterious mutation in any of the study-defined HRR genes [ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCF, FANCM, NBN (NBS1), PALB2, RAD51, RAD51B (RAD51L1), RAD54L, RPA1) defined as the full eligible population (FEP). The primary analysis population (PAP) is defined by a subset of genes [ATM, ATR, BRCA1, BRCA2, PALB2]. Pts have platinum sensitive disease (at least stable disease on platinum doublet) and progressed on most recent line of systemic therapy, a Zubrod performance status of 0-1, adequate organ function, and not have been previously exposed to a PARP inhibitor and not be on systemic therapy within 21 days of registration. A 2-stage design with exact 93% power and 1-sided 0.07 level type I error required enrollment of 40 patients in the PAP in order to rule out an ORR of 15% or less if the true ORR is 35% or greater. At least 3 or more responses were needed in the first 20 pts in order to proceed to full enrolment of 40 pts in the PAP. The total accrual goal was 60 FEP assuming 67% of patients would be in the PAP. Results: The study enrolled 51 patients of whom 47 are eligible and analyzable for response (FEP) with 24 in the PAP. In the FEP, median age 66.7 yrs; M/F 39/8 (83/17%); 85% White and 15% Black; 77% of the pts received at least 1 prior line of treatment for stage IV. The study was closed for futility with only one response in the PAP. In the PAP (n = 24, median age 68 yrs), ORR was 4% (95%CI: 0, 21) and DCR was 54% (95%CI: 33, 74); median PFS of 2.4 months (95%CI: 1.5-2.8) and median OS was 5.2 months (95%CI: 3.8-10, 7). There were five responders in the FEP with ORR of 11%; DCR of 53% and median DoR was 1.8 months (95% CI: 1.3, 4.2); median PFS was 2.5 months (95%CI: 1.6-3.0) and median OS was 5.7 months (95% CI: 4.5-8.7). The most frequent grade ≥3 adverse event in the FEP were: Anemia (14.9%), thrombocytopenia (12.8%); lymphopenia (8.5%) and nausea (6.4%). Conclusions: S1400G failed to show sufficient level of efficacy for talazoparib in a biomarker defined subset of squamous lung cancer with HRRD. There were no new safety signals and hematologic toxicities were the most frequent adverse events. Clinical trial information: NCT02154490.

New Treatment Options in Advanced Squamous Cell Lung Cancer

The past few years have witnessed a rapid shift in the treatments for patients with squamous cell lung cancers (SQCLCs) after the U.S. Food and Drug Administration approval of a number of immune checkpoint inhibitors as second-line therapies for patients with non-small cell lung cancers. These series of approvals marked the first substantial improvement in overall survival for patients with SQCLC in over a decade. Further gains have been made more recently with the incorporation of immune checkpoint inhibition in the first-line setting, either as monotherapy or in combination with chemotherapy. These advances have, however, exposed existing deficiencies in the management of this disease. Despite a deeper understanding of the genomic alterations that characterize SQCLCs and years of trial work targeting these alterations, personalized therapies remain out of hand. Future studies will continue to focus on identifying targeted approaches to expand the treatment options for our patients.

Clinical Experience of Immunotherapy Treatment: Efficacy and Toxicity Analysis of the Compassionate Use Program of Nivolumab in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer

Background: Anti-PD1 monoclonal antibody nivolumab is an approved therapy option for the treatment of advanced squamous cell non-small cell lung cancer (SQ-NSCLC) patients. Data outside clinical trials about therapy efficacy and safety in later therapy line treatments have rarely been described until now. Methods: We performed a retrospective data analysis of patients who were enrolled into the nivolu­mab Compassionate Use Program (CUP) in Germany. Sufficient clinical data of 40 patients were available for efficacy and safety analysis. Results: Overall, 47.5% of all treated patients were not affected by any adverse events (AEs); 17.5% of patients suffered from severe AEs. The 1-year survival rate was 61.3%. Estimated median progression-free survival (PFS) was 5.3 months. Patients who received nivolumab as third or later therapy line treatment (77.5%) achieved similar median PFS and 12-month overall survival rate of 52%. Conclusion: Our findings of immunotherapy treatment outside clinical trials support the results of studies in the past and confirm the efficacy and favorable toxicity profile of nivolumab treatment in advanced SQ-NSCLC patients. In addition, we can present some rarely described information about nivolumab treatment of heavily pretreated patients, which provides some evidence that immunotherapy could also be useful in later therapy lines.

Italian Cohort of Nivolumab Expanded Access Program in Squamous Non-Small Cell Lung Cancer: Results from a Real-World Population.

Nivolumab has shown a survival benefit compared with docetaxel as second-line treatment for patients with previously treated advanced squamous non-small cell lung cancer (NSCLC) in a randomized phase III trial. The experiences of patients and physicians in routine clinical practice are often different from those in a controlled clinical trial setting. We present data from the entire Italian cohort of patients with squamous NSCLC enrolled in a worldwide nivolumab NSCLC expanded access program. Patients with pretreated advanced squamous NSCLC received nivolumab 3 mg/kg every 2 weeks for up to 24 months. Safety was monitored throughout; efficacy data collected included objective tumor response, date of progression, and survival information. The Italian cohort comprised 371 patients who received at least one dose of nivolumab. In the overall population, the objective response rate (ORR) was 18%, the disease control rate (DCR) was 47%, and median overall survival (OS) was 7.9 months (95% confidence interval 6.2-9.6). In subgroup analyses, ORR, DCR, and median OS were, respectively, 17%, 48%, and 9.1 months in patients previously treated with two or more lines of therapy (n = 209) and 8%, 40%, and 10.0 months in patients treated beyond disease progression (n = 65). In the overall population, the rate of any-grade and grade 3-4 adverse events was 29% and 6%, respectively. Treatment-related adverse events led to treatment discontinuation in 14 patients (5%). There were no treatment-related deaths. To date, this report represents the most extensive clinical experience with nivolumab in advanced squamous NSCLC in current practice outside the controlled clinical trial setting. These data suggest that the efficacy and safety profiles of nivolumab in a broad, real-world setting are consistent with those obtained in clinical trials. Nivolumab is approved in the U.S. and Europe for the treatment of advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. In this cohort of Italian patients with previously treated, advanced squamous NSCLC treated in a real-world setting as part of the nivolumab expanded access program, the efficacy and safety of nivolumab was consistent with that previously reported in nivolumab clinical trials.

186TiP - An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy: EDEN trial

186TiP - An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy: EDEN trial

Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced squamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

121 Background: Squamous Non-small cell lung cancer (NSCLC) accounts for ~30% of lung cancers, and long-term survival remains poor for advanced disease. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 3 RCTs (Keynote – 407, IMpower – 131, and Govindan et al) including 1991 patients with advanced squamous NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, or atezolizumab, while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.71 (95% CI: 0.56-0.9; P = 0.005), the pooled HR for OS was 0.84 (95% CI: 0.68-1.04; P = 0.11), and the pooled RR for ORR was 1.19 (95 CI: 0.9-1.56; P = 0.22). The pooled RRs for all-grade AEs and high-grade AEs were 1.17 (95% CI: 0.99-1.39; P = 0.07) and 1.36 (95% CI: 1.19-1.56; P = 0.0001), respectively. Conclusions: The combined chemo-immunotherapy improves PFS without significant improvement in OS &amp; ORR compared to standard chemotherapy for the first-line treatment of advanced squamous NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.

Phase II Study of a Bi-Weekly Chemotherapy Regimen of Combined Liposomal Paclitaxel and Nedaplatin for the Treatment of Advanced Squamous Cell Lung Cancer

The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a 4-week cycle. Each patient received two to six cycles of chemotherapy, consistent with the regimen of combined liposomal paclitaxel and nedaplatin. The total effective rate of this chemotherapy program was 37.5%. The median progression-free survival time was 8.5 months (95% confidence interval: 7.8–9.2). The median survival time was 16 months (95% confidence interval: 14.1–17.9). The main adverse event was myelosuppression. Grade 3 leukopenia was noted in seven patients (13.5%), and no grade 4 leukopenia was observed. Grade 3 anemia was noted in four patients (7.7%), and no grade 4 anemia was observed. In addition, no grade 2 or higher thrombocytopenia and no grade 3 or 4 non-bone marrow toxicity was detected. The bi-weekly program of liposomal paclitaxel combined with nedaplatin is effective for the treatment of advanced squamous cell lung cancer, with high safety and few adverse events. However, additional studies are warranted to confirm these results. The trial was registered under the number ChiCTR-OIN-17011423.

A Phase II Study of Tailored-dose S-1 Plus Carboplatin Followed by Maintenance S-1 for Advanced Squamous Cell Lung Cancer: OSAKA-LCSG 1102

Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC. Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety. Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable. Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Development of treatment options for Chinese patients with advanced squamous cell lung cancer: focus on afatinib.

Lung cancer is the leading cause of cancer death in China, and approximately one third of these cancers are squamous cell carcinoma (SqCC) of the lung. Ethnic diversity and country-specific environmental factors can account for interindividual variations in response to and tolerability of anticancer therapies. Although several targeted therapies have recently been approved for patients with relapsed/refractory SqCC of the lung, only afatinib, an irreversible ErbB family blocker, has data of Chinese patients. In the Phase III LUX-Lung 8 trial, afatinib demonstrated a significant clinical benefit vs the reversible first-generation EGFR tyrosine kinase inhibitor erlotinib in both the overall population and the Chinese subset, with a manageable safety profile. Emerging biomarker data from LUX-Lung 8 suggest that patients with ErbB mutations, especially ErbB2, and those classified as “good” in the VeriStrat® proteomic test, may benefit from afatinib treatment in particular, regardless of ethnicity, and may get a long-term response. In conclusion, afatinib is a valid second-line option for Chinese patients with SqCC of the lung, and specific biomarkers may help guide in treatment decision-making. Ongoing studies will provide further guidance on afatinib’s place in the treatment algorithm, alongside the other novel targeted therapies.

OA08 Efficacy and Safety of Sintilimab Combined with 1st Line Chemotherapy in Advanced Squamous Cell Non-small Cell Lung Cancer

OA08 Efficacy and Safety of Sintilimab Combined with 1st Line Chemotherapy in Advanced Squamous Cell Non-small Cell Lung Cancer

First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995-2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

Nivolumab in never-smokers with advanced squamous non-small cell lung cancer: Results from the Italian cohort of an expanded access program.

Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer. Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored. Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7-20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2-9.6), respectively, in the overall expanded access program population. Any-grade and grade 3-4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3-4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall. Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.

501P - Phase II study of nedaplatin plus amrubicin in patients with untreated, advanced or relapsed squamous cell lung cancer

501P - Phase II study of nedaplatin plus amrubicin in patients with untreated, advanced or relapsed squamous cell lung cancer

1434P - A phase II study of nedaplatin and nab-paclitaxel for patients with previously untreated advanced squamous cell lung cancer (KRSG1302)

ABSTRACT Aim: Nedaplatin, a second-generation platinum derivative, is efficacious in the treatment of non-small cell lung cancer (NSCLC), especially squamous cell carcinoma. Previous studies investigating a combination of nedaplatin and paclitaxel (N/P) in the treatment of NSCLC showed promising outcomes, but there was no sufficient data in the treatment of squamous cell lung cancer. Here, we aimed to elucidate the efficacy and toxicity of N/P for previously untreated advanced squamous cell lung cancer. Methods: The eligibility criteria were no prior chemotherapy; stage IIIB squamous cell lung cancer with no indications for radiotherapy or stage IV squamous cell lung cancer; a performance status (PS) of 0–1; age > 20 years; and adequate hematologic, hepatic, and renal function. Patients received nedaplatin (80 mg/m2, day 1) and paclitaxel (90 mg/m2, days 1 and 8) every 3 weeks. The primary endpoint was tumor response, which was measured using Response Evaluation Criteria in Solid Tumors 1.1. Tumor responses were confirmed by two extramural reviewers. Results: Eighteen patients were enrolled in this study, and all were evaluable for toxicity and efficacy. The median patient age was 68 years (range, 49–77 years). Three and 15 patients had PS 0 and PS 1, respectively, and 7 and 11 patients had stage IIIB disease and stage IV disease, respectively. The median number of treatment cycles was 6 (range, 2–6). Complete response, partial response, and stable disease were noted in 1, 12, and 5 patients, respectively, yielding a response rate of 72.2% (95%confidence interval [CI]: 46.5–90.3). The median progression-free survival was 7.5 months (95%CI: 6.1–10.4), and the median survival time was 30.9 months (95%CI: 9.9–46.4). The grade 3 and 4 toxicities observed during all cycles were leukopenia (4 and 0 patients, respectively), anemia (4 and 1 patients, respectively), thrombocytopenia (2 and 1 patients, respectively), and neutropenia (8 and 2 patient, respectively). Although grade 2 pneumonitis occurred in 1 patient, there was no severe non-hematologic toxicity. Conclusions: N/P appears to be safe and efficacious in patients with untreated advanced squamous cell lung cancer. Disclosure: All authors have declared no conflicts of interest.