***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 .  Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer .  Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Aims and Background The theraputic role of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) is controversial because of its potentially detrimental action on host anticancer defenses . On the contrary , IL-2 would seem to prolong survival time by improving the immune status , even though it is generally less effective in determining tumor regression in NSCLC . Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones , such as the pineal hormone melatonin ( MLT ) . On this basis , a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC . Methods The study included 60 patients with locally advanced or metastatic NSCLC , who were r and omized to receive immunotherapy or chemotherapy .  The immunotherapy consisted of IL-2 ( 3 million IU/day subcutaneously for 6 days/week for 4 weeks ) and MLT ( 40 mg/day orally every day , starting 7 days before IL-2 ) ; in nonprogressing patients , a second cycle was repeated after a 21-day rest period , then they underwent a maintenance period consisting of one week of therapy every month until progression . Chemotherapy consisted of cisplatin ( 20 mg/m2 ) and etoposide ( 100 mg/m2)/day intravenously for 3 days ; cycles of chemotherapy were repeated every 21 days until progression . Results No complete response was obtained . A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy . The difference was not significant . In contrast , the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy .  Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy . Conclusions This r and omized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC Background Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma ( NSCLC ) . These promising findings prompted the phase III study , INSPIRE , in patients of East-Asian ethnicity . East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC . The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population . Methods / design The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care ( BSC ) , as compared to placebo plus BSC , on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria following primary chemoradiotherapy . Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide ( 300 mg/m2 ) 3 days before the first L-BLP25 vaccination , with a corresponding intravenous infusion of saline to be given in the control arm . A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study . Discussion The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population . It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available . Study numberEMR 63325 - 012Trial Registration Clinical trials.gov reference : To evaluate the feasibility , safety , and efficacy of vaccination with autologous tumor cells genetically modified with an adenoviral vector ( Ad-GM ) to secrete human granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , we conducted a phase I/II multicenter trial in patients with early and advanced stage non-small-cell lung cancer ( NSCLC ) .  Vaccines were generated from autologous tumor harvests . Intradermal injections were given every 2 weeks for a total of three to six vaccinations . Tumors were harvested from 83 patients , 20 with early-stage NSCLC and 63 with advanced- stage NSCLC ; vaccines were successfully manufactured for 67 patients , and 43 patients were vaccinated . The most common toxicity was a local injection-site reaction ( 93 % ) . Three of 33 advanced-stage patients , two with bronchioloalveolar carcinoma , had durable complete tumor responses ( lasting 6 , 18 , and > or=22 months ) . Longer survival was observed in patients receiving vaccines secreting GM-CSF at more than 40 ng/24 h per 10(6 ) cells ( median survival = 17 months , 95 % confidence interval [ CI ] = 6 to 23 months ) than in patients receiving vaccines secreting less GM-CSF ( median survival = 7 months , 95 % CI = 4 to 10 months ) ( P = .028 ) , suggesting a vaccine dose-related survival advantage Summary A phase-II r and omized trial has been undertaken in 49 patients with operable lung cancer , to determine the effect of a single IV infusion of killed C. parvum vaccine as an adjuvant to surgery . The number of patients was insufficient to provide a decisive result , but analysis 6 years after the last patient was admitted shows that the adjuvant therapy certainly did not shorten , and may well have prolonged , survival . Of the patients with squamous cell carcinoma who were alive 1 year after operation all except one in the C. parvum-treated group were alive 4 years later , whereas five in the control group died during this interval . Judgement concerning the value of IV administration of CP as adjuvant therapy in patients with operable lung cancer should be deferred until further evidence is available Purpose : Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes . Result ing clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions ( progressive disease ) . Response Evaluation Criteria in Solid Tumors or WHO criteria , design ed to detect early effects of cytotoxic agents , may not provide a complete assessment of immunotherapeutic agents . Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required . Experimental Design : The phase II clinical trial program with ipilimumab , an antibody that blocks CTL antigen-4 , represents the most comprehensive data set available to date for an immunotherapeutic agent . Novel immune therapy response criteria proposed , based on the shared experience from community workshops and several investigators , were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma . Results : Ipilimumab monotherapy result ed in four distinct response patterns : ( a ) shrinkage in baseline lesions , without new lesions ; ( b ) durable stable disease ( in some patients followed by a slow , steady decline in total tumor burden ) ; ( c ) response after an increase in total tumor burden ; and ( d ) response in the presence of new lesions . All patterns were associated with favorable survival . Conclusion : Systematic criteria , design ated immune-related response criteria , were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria . Further prospect i ve evaluations of the immune-related response criteria , particularly their association with overall survival , are warranted . ( Clin Cancer Res 2009;15(23):7412–20 BACKGROUND Tecemotide is a MUC1-antigen-specific cancer immunotherapy . The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy .  Here , we attempted to gain further insight into the effects of tecemotide in START . PATIENTS AND METHODS START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer . We present up date d overall survival ( OS ) data and exploratory analyses of OS for baseline biomarkers : soluble MUC1 ( sMUC1 ) , antinuclear antibodies ( ANA ) , neutrophil/lymphocyte ratio ( NLR ) , lymphocyte count , and HLA type . RESULTS Up date d OS data are consistent with the primary analysis : median 25.8 months ( tecemotide ) versus 22.4 months ( placebo ) ( HR 0.89 , 95 % CI 0.77 - 1.03 , P = 0.111 ) , with ∼20 months additional median follow-up time compared with the primary analysis . Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinical ly relevant prolonged OS  with tecemotide versus placebo ( 29.4 versus 20.8 months ; HR 0.81 , 95 % CI 0.68 - 0.98 , P = 0.026 ) . No improvement was seen with sequential chemoradiotherapy . High sMUC1 and ANA correlated with a possible survival benefit  with tecemotide ( interaction P = 0.0085 and 0.0022 ) and might have future value as biomarkers . Interactions between lymphocyte count , NLR , or prespecified HLA alleles and treatment effect were not observed . CONCLUSION Up date d OS data support potential treatment benefit with tecemotide  in patients treated with concurrent chemoradiotherapy . Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit . CLINICAL TRIALSGOV NUMBER NCT00409188 Purpose We conducted a phase III r and omized controlled trial ( RCT ) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy . The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy . Patients and methods Between April 2007 and July 2012 , 103 postsurgical non-small cell lung cancer patients were r and omly assigned to receive either chemo-immunotherapy ( group A ) or chemotherapy ( group B ) . The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients ’ own regional lymph nodes . Results The 2-year overall survival rates in groups A and B were 93.4 and 66.0 % , and the 5-year rates were 8 
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The current literature does not provide evidence that suggests a survival benefit from adding immunotherapy ( excluding checkpoint inhibitors ) to conventional curative surgery or radiotherapy , for patients with localised NSCLC ( stages I to III ) .
The addition of vaccine-based immunotherapy might increase the risk of adverse events .