***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 We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy . METHODS In the GeparQuinto r and omised phase 3 trial , patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7 , 2007 , and July 9 , 2010 . Patients were eligible if their tumours were classified as cT3/4a-d , or hormone receptor (HR)-negative , HR-positive with clinical ly node-positive and cT2 disease ( cT2 cN+ ) , or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease ( cT1 pN(SLN+ ) ) . Patients were r and omly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC ( epirubicin [ 90 mg/m(2 ) intravenously ] plus cyclophosphamide [ 600 mg/m(2 ) intravenously ] , every 3 weeks ) , and four cycles of docetaxel ( 100 mg/m(2 ) intravenously every 3 weeks ) with either trastuzumab ( 6 mg/kg intravenously , with a starting loading dose of 8 mg/kg , for eight cycles , every 3 weeks ) or lapatinib ( 1000 - 1250 mg per day orally ) throughout all cycles before surgery . R and omisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site , HR status , and extent of disease ( cT1 - 3 cN0 - 2 vs T4 or N3 ) . The primary endpoint was pathological complete response ( defined as ypT0 and ypN0 ) and was analysed in all patients who received at least one cycle of EC . Participants and investigators were not masked to treatment assignment . Pathologists in centres assessing surgery outcomes were masked to group assignment . This trial is registered with Clinical Trials.gov , number NCT00567554 . FINDINGS Of 620 eligible patients , 309 were r and omly assigned to chemotherapy with trastuzumab ( ECH-TH group ) and 311 to chemotherapy with lapatinib ( ECL-TL group ) . Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery . 93 ( 30·3 % ) of 307 patients in the ECH-TH group and 70 ( 22·7 % ) of 308 patients in the ECL-TL group had a pathological complete response ( odds ratio [ OR ] 0·68 [ 95%CI 0·47 - 0·97 ] ;  p=0·04 )  . Chemotherapy with trastuzumab was associated with more oedema ( 119 [ 39·1 % ] vs 88 [ 28·7 % ] ) and dyspnoea ( 90 [ 29·6 % ] vs 66 [ 21·4 % ] ) , and ECL-TL with more diarrhoea ( 231 [ 75·0 % ] vs 144 [ 47·4 % ] ) and skin rash ( 169 [ 54·9 % ] vs 97 [ 31·9 % ] ) . 43 ( 14·0 % ) patients discontinued in the ECH-TH group and 102 ( 33·1 % ) in the ECL-TL group . 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group . INTERPRETATION This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate  with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab . Unless long-term outcome data show different results , lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy . FUNDING GlaxoSmithKline , Roche , and Sanofi-Aventis BACKGROUND We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined .  Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting Background : Phase-IV , open-label , single-arm study ( NCT01203917 ) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV , epidermal growth factor receptor ( EGFR ) mutation-positive non-small-cell lung cancer ( NSCLC ) . Methods : Treatment : gefitinib 250 mg day−1 until progression . Primary endpoint : objective response rate ( ORR ) . Secondary endpoints : disease control rate ( DCR ) , progression-free survival ( PFS ) , overall survival ( OS ) and safety/tolerability . Pre-planned exploratory objective : EGFR mutation analysis in matched tumour and plasma sample s. Results : Of 1060 screened patients with NSCLC ( 859 known mutation status ; 118 positive , mutation frequency 14 % ) , 106 with EGFR sensitising mutations were enrolled ( female 70.8 % ; adenocarcinoma 97.2 % ; never-smoker 64.2 % ) . At data cutoff : ORR 69.8 % ( 95 % confidence interval ( CI ) 60.5–77.7 ) , DCR 90.6 % ( 95 % CI 83.5–94.8 ) , median PFS 9.7 months ( 95 % CI 8.5–11.0 ) , median OS 19.2 months ( 95 % CI 17.0–NC ; 27 % maturity ) . Most common adverse events ( AEs ; any grade ): rash ( 44.9 % ) , diarrhoea ( 30.8 % ) ; CTC ( Common Toxicity Criteria ) grade 3/4 AEs : 15 % ; SAEs : 19 % . Baseline plasma 1 sample s were available in 803 patients ( 784 known mutation status ; 82 positive ; mutation frequency 10 % ) . Plasma 1 EGFR mutation test sensitivity : 65.7 % ( 95 % CI 55.8–74.7 ) . Conclusion : First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC . Plasma sample s could be considered for mutation analysis if tumour tissue is unavailable Dual epidermal growth factor receptor ( EGFR ) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models . Ki-67 labeling index ( LI ) has prognostic and predictive value and can be used to screen drugs ' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer . We conducted a r and omized , placebo-controlled trial of lapatinib ( 1500 mg/d ) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker ( including the primary endpoint , Ki-67 LI ) and clinical activity in invasive breast cancer , adjacent ductal intraepithelial neoplasia ( DIN , which comprises ductal carcinoma in situ and atypical ductal hyperplasia ) , and distant ductal hyperplasia without atypia ( DH ) . Ki-67 LI increased progressively in association with disease stage , increasing in the placebo arm , for example , by medians of 3 % in DH to 20 % in DIN to 30 % in invasive cancer . Ki-67 LI in cancer tissue decreased by a mean ( ±SD ) of 9.3 % ( ±34.2 ) in the lapatinib arm and increased by 15.1 % ( ±30.9 ) in the placebo arm ( P = 0.008 ) . Compared with placebo , lapatinib reduced Ki-67 significantly more in ER-negative tumors ( by 34.8 % ; P = 0.01 ) but not significantly more in ER-positive tumors ( by 12.3 % ; P = 0.2 ) and reduced Ki-67 more ( nonsignificantly ) in cytosol PTEN-overexpressing tumors ( P = 0.057 ) . The prevalence of DIN in post-treatment surgical specimens of both arms was similar ( 70%–76 % ) , with a median Ki-67 of 15 % ( range , 5%–35 % ) on lapatinib versus 20 % ( 5%–60 % ) on placebo ( P = 0.067 ) . The prevalence of DH also was similar in both arms ( > 90 % ) , with a median Ki-67 of 1 % ( 1%–7 % ) on lapatinib versus 3 % ( 1%–5 % ) on placebo ( P = 0.006 ) . Other results of lapatinib versus placebo , respectively , were as follows : Median tumor diameter at surgery of 18 mm ( 11 mm–57 mm ) versus 24 mm ( 10 mm–37 mm ; P = 0.009 ) ; partial response of 13.6 % versus 3.7 % , stable disease of 59.1 % versus 40.7 % , and progression of 27.3 % versus 55.6 % ( P-trend = 0.035 ) . In conclusion 
    Output:
    
Exploratory subgroup analysis showed no effect of treatment regimen on the RRs of the relevant adverse events .
Our meta- analysis has demonstrated that lapatinib is associated with a significantly increased risk of all- grade skin rash , h and foot skin reaction and pruritus .