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1.
J Immunother ; 46(1): 22-26, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36472582

ABSTRACT

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting. The value of the model in predicting overall survival and progression-free survival was statistically significant and clinically meaningful, with an overall survival rate at 12 months of 73% vs. 44% (P<0.0001), and median progression-free survival of 11.6 (95% CI: 9.1-14.1) months versus 4.8 (95% CI: 2.7-7.0) months (P=0.002), respectively, for patients belonging to the favorable group (score 0-1) versus the unfavorable (score 2-4). Further development will be represented by the gut microbiome analysis according to the drug-based model classification and to the outcome of patients to ICI therapy to demonstrate the link between drug exposure and immune sensitivity.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Ipilimumab/therapeutic use , Nivolumab/therapeutic use , Compassionate Use Trials , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/drug therapy , Pharmaceutical Preparations , Prognosis , Prospective Studies , Kidney Neoplasms/diagnosis , Kidney Neoplasms/drug therapy , Communication
2.
Eur Urol ; 83(1): 82-89, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36216658

ABSTRACT

BACKGROUND: Platinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors. OBJECTIVE: To compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT. DESIGN, SETTING, AND PARTICIPANTS: Meet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease). INTERVENTION: Patients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate). RESULTS AND LIMITATIONS: Fifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49-1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3-4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely. CONCLUSIONS: Addition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population. PATIENT SUMMARY: In this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Aged , Carcinoma, Transitional Cell/drug therapy , Platinum/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Progression-Free Survival , Disease Progression , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Maintenance Chemotherapy
3.
Lancet Oncol ; 23(7): 888-898, 2022 07.
Article in English | MEDLINE | ID: mdl-35688173

ABSTRACT

BACKGROUND: In the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety. METHODS: This open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT03141177. FINDINGS: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death). INTERPRETATION: With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Renal Cell , Kidney Neoplasms , Anilides , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Follow-Up Studies , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Pyridines , Sunitinib/therapeutic use
4.
N Engl J Med ; 384(9): 829-841, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33657295

ABSTRACT

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).


Subject(s)
Anilides/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Nivolumab/administration & dosage , Pyridines/administration & dosage , Sunitinib/therapeutic use , Adult , Aged , Aged, 80 and over , Anilides/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Renal Cell/mortality , Female , Humans , Intention to Treat Analysis , Kidney Neoplasms/mortality , Male , Middle Aged , Nivolumab/adverse effects , Progression-Free Survival , Proportional Hazards Models , Pyridines/adverse effects , Quality of Life , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Sunitinib/adverse effects , Survival Analysis
5.
PLoS One ; 13(7): e0199642, 2018.
Article in English | MEDLINE | ID: mdl-29979712

ABSTRACT

BACKGROUND: Results from phase III clinical trial CheckMate 025 have established nivolumab as the standard of care for treatment of metastatic renal-cell carcinoma (mRCC) after VEGF inhibitor failure; however, elderly patients are under-represented in the registration trial and little is known about the activity of nivolumab in this subgroup. The purpose of the Expanded Access Program was to provide nivolumab to patients with mRCC who had progressed despite treatment with other agents that were considered standard of care. METHODS: Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months or until progression or unacceptable toxicity. The current analysis included all patients from the EAP Italian cohort who had received ≥1 dose of nivolumab. Adverse events (AEs) were monitored using Common Terminology Criteria for Adverse Events v4.0. RESULTS: A total of 389 patients with advanced RCC were enrolled in the Italian cohort of the EAP and treated with nivolumab. Of these patients, 125 (32%) were at least 70 years of age and 70 (18%) were at least 75 years of age. Efficacy with nivolumab in the elderly patients was similar to that observed in the overall EAP population and in the CheckMate 025 trial. Safety was comparable between the elderly patients and the overall EAP population, and was consistent with what previously reported. CONCLUSION: The final results suggest that elderly patients with pretreated metastatic RCC may benefit from therapy with nivolumab.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Nivolumab/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Carcinoma, Renal Cell/mortality , Female , Humans , Italy , Kidney Neoplasms/mortality , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Nivolumab/administration & dosage , Nivolumab/adverse effects , Retreatment , Survival Analysis , Treatment Outcome
6.
Future Oncol ; 11(22): 3083-90, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26437324

ABSTRACT

BACKGROUND: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. PATIENTS & METHODS: All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. RESULTS: Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. CONCLUSIONS: Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. The interest in this strategy may be increased because of the showed efficacy of early DCT chemotherapy in patients with bulky disease (CHAARTED study) and the potential lower efficacy of the new hormonal agents abiraterone acetate and enzalutamide when used in a immediate sequencing.


Subject(s)
Antineoplastic Agents/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Taxoids/therapeutic use , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Disease Progression , Docetaxel , Follow-Up Studies , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/mortality , Retreatment , Retrospective Studies , Taxoids/administration & dosage , Treatment Outcome
7.
Semin Oncol ; 42(3): 495-505, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25965369

ABSTRACT

Genitourinary (GU) tumors, and in particular renal cell and prostate cancer, represent one of the most dynamic areas in oncology from the scientific point of view. One of the most recent treatment approaches for GU tumors has focused on a series of molecules known as immune checkpoints and the possibility of manipulating immune responses against tumor cells by blocking these molecules with monoclonal antibodies (mAbs). Cytotoxic T lymphocyte antigen-4 (CTLA-4), and the immune checkpoint inhibitor mAbs ipilimumab and tremelimumab, represent the prototypes of this new growing class of agents called immunomodulating antibodies, while programmed death/ligand 1 (PD-1/PD-L1) also has garnered a significant interest as a new immune checkpoints to target in urothelial cancer, with the anti-PD-1/PD-L1 inhibitor mAbs nivolumab, MPDL-3280, and BMS-936559 as the first agents tested. Here we report the encouraging initial data observed in GU cancers with this new class of agents, which have reinforced the interest of investigating the therapeutic potential of the immune checkpoint modulators in large controlled trials.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Immunologic Factors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/immunology , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/immunology , Clinical Trials as Topic , Humans , Immunologic Factors/pharmacology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/immunology , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/immunology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/immunology
8.
Expert Rev Anticancer Ther ; 14(11): 1283-94, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25353258

ABSTRACT

Although docetaxel is still considered a mainstay of treatment in metastatic castrate-resistant prostate cancer (mCRPC), in the last few years, new agents have been developed to improve survival in this setting and reach a possible optimal personalized treatment strategy. In this paper, we provide a personal view and an algorithm for mCRPC patients, according to available evidence, personal opinion and experience. Abiratone acetate, cabazitaxel, radium-223, sipuleucel-T and enzalutamide, together with docetaxel, have demonstrated a survival benefit in these patients. The use of rechallenge with docetaxel in mCRPC patients with disease progression after a first response has been considered. These new agents complicated the scenario and posed the challenge to move from the old sequential to a new algorithm-based approach. At this stage, the algorithm is necessarily based on experts' opinion, since the efficacy of a single agent in a specific setting has not been validated by sequential trials.


Subject(s)
Algorithms , Androgen Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm , Prostatic Neoplasms, Castration-Resistant/drug therapy , Docetaxel , Humans , Male , Prostatic Neoplasms, Castration-Resistant/diagnosis , Randomized Controlled Trials as Topic/methods , Taxoids/therapeutic use , Tissue Extracts/therapeutic use
9.
Crit Rev Oncol Hematol ; 89(3): 386-93, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24309065

ABSTRACT

Metastatic renal cell carcinoma (mRCC), considered almost an orphan disease only six years ago, appears today a very dynamic pathology. The recently switch to the actual overcrowded scenario defined by seven active drugs has driven physicians to an incertitude status, due to difficulties in defining the best possible treatment strategy. This situation is mainly related to the absence of predictive biomarkers for any available or new therapy. Such issue, associated with the nearly absence of published face-to-face studies, draws a complex picture frame. In order to solve this dilemma, decisional algorithms tailored on drug efficacy data and patient profile are recognized as very useful tools. These approaches try to select the best therapy suitable for every patient profile. On the contrary, the present review has the "goal" to suggest a reverse approach: basing on the pivotal studies, post-marketing surveillance reports and our experience, we defined the polarizing toxicity (the most frequent toxicity in the light of clinical experience) for every single therapy, creating a new algorithm able to identify the patient profile, mainly comorbidities, unquestionably unsuitable for each single agent presently available for either the first- or the second-line therapy. The GOAL inverse decision-making algorithm, proposed at the end of this review, allows to select the best therapy for mRCC by reducing the risk of limiting toxicities.


Subject(s)
Algorithms , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Practice Patterns, Physicians' , Antineoplastic Agents/toxicity , Carcinoma, Renal Cell/pathology , Humans , Kidney Neoplasms/pathology , Neoplasm Metastasis
10.
Tumori ; 99(6): 285e-7e, 2013.
Article in English | MEDLINE | ID: mdl-24503805

ABSTRACT

We present the case of a 51-year-old woman with a follicular variant of papillary thyroid carcinoma. After surgery she experienced a relapse. Chemotherapy treatment led only to disease stabilization. In August 2009, we decided to start therapy with sunitinib 50 mg daily in an intermittent schedule (4 weeks on/2 weeks off). A CT scan after 3 months of treatment showed partial remission of disease according to the RECIST criteria. The patient continued sunitinib until January 2011, when CT evidenced progression in the mediastinal lymph nodes and pleura. Genetic analyses were carried out to determine if the clinical response in our patient was correlated with the presence of RET or BRAF mutations. No RET/PTC rearrangements or BRAF-V600E mutation, which are the two most common genetic alterations detected in papillary thyroid carcinoma, were found. It can be hypothesized that the activity of sunitinib in this patient was due to its antiangiogenic properties.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/pathology , Carcinoma/drug therapy , Carcinoma/pathology , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pyrroles/therapeutic use , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma/blood , Carcinoma/surgery , Carcinoma, Papillary/blood , Carcinoma, Papillary/surgery , Cisplatin/administration & dosage , Disease Progression , Doxorubicin/administration & dosage , Drug Administration Schedule , Etoposide/administration & dosage , Fatal Outcome , Female , Humans , Indoles/administration & dosage , Indoles/pharmacology , Lung Neoplasms/blood , Lung Neoplasms/diagnosis , Lymphatic Metastasis , Mediastinum , Middle Aged , Neoplasm Recurrence, Local/blood , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-ret/genetics , Pyrroles/administration & dosage , Pyrroles/pharmacology , Sunitinib , Thyroglobulin/blood , Thyroid Cancer, Papillary , Thyroid Neoplasms/blood , Thyroid Neoplasms/surgery , Tomography, X-Ray Computed
12.
Lung Cancer ; 54 Suppl 2: S19-24, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17056151

ABSTRACT

Lung cancer remains the leading cause of cancer-related mortality in the western world. Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of these thoracic malignancies, with 1.2 million new cases diagnosed worldwide each year. The vast majority of NSCLC patients present with disease that is beyond the scope of surgical cure and are, therefore, candidates for palliative chemotherapy, which has been the subject of intensive investigation in recent years. Although platinum-based therapies modestly improve survival and palliate some tumour-related symptoms in patients with locally advanced or metastatic NSCLC, at times the chemotherapy-related side effects outweigh the benefits. Consequently, the identification of new regimens that maintain the same level of efficacy as platinum-based combinations but offer a better toxicity profile is a key goal in this important area of medicine.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cytotoxins/therapeutic use , Lung Neoplasms/drug therapy , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Bevacizumab , Humans , Treatment Outcome
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