Metastatic Papillary Renal Cell Carcinoma Research Articles

Histopathologic Diagnosis of Pleural Metastasis of Renal Cell Carcinoma Using Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful, safe diagnostic modality for evaluating mediastinal and hilar lymphadenopathy. We report a 51-year-old male who presented with a left renal mass and multiple pleural masses without lung parenchymal lesions. The pleural masses were thought to be metastatic tumors or malignant mesothelioma. The patient underwent two percutaneous needle biopsies of the pleural mass, but the specimens were insufficient for a histopathological diagnosis. Because one pleural mass was adjacent to the right main bronchus, we decided to perform EBUS-TBNA for the pleural mass. As a result, sufficient core tissue was obtained with no complications, and the histopathological findings were consistent with metastatic papillary renal cell carcinoma. To our knowledge, this is the f irst case of using EBUS-TBNA for a pleural mass.

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Open-label phase II trial of everolimus monotherapy in treatment-naive patients with advanced papillary renal cell carcinoma.

TPS234 Background: Papillary renal cell carcinoma (RCC) is genetically and morphologically distinct from other RCCs, and accounts for up to 10% of RCC diagnoses. All RCC histologies are generally resistant to chemotherapy. Newer targeted treatment approaches have demonstrated clinical benefit in patients with clear cell RCC, but options for the treatment of papillary RCC remain limited. Everolimus, an oral mTOR inhibitor, has demonstrated efficacy in the pivotal RECORD-1 study in patients with mRCC with a “clear cell component” histology that progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy, and everolimus is now indicated for use in this patient population. Because mTOR is also aberrantly activated in papillary RCC, mTOR inhibition presents a novel means for targeted therapy in papillary RCC. The ongoing RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe) trial is evaluating the efficacy and safety of everolimus monotherapy in treatment-naive patients with advanced papillary RCC. Methods: RAPTOR is an open-label, single-arm, non-randomized, single-stage, multicenter phase II trial currently recruiting participants. Up to 60 patients ≥18 years of age with a centrally confirmed histologic diagnosis of advanced type I or II metastatic papillary RCC, ≥1 measurable baseline lesion as per RECIST criteria, ECOG performance status of 0 or 1, and adequate liver, renal, and bone marrow function will be enrolled. Patients who have received prior systemic RCC therapy (ie, sorafenib, sunitinib, bevacizumab) are excluded. Patients will receive everolimus 10 mg/d orally until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. The primary study endpoint is PFS rate at 6 months. Disease control rate, objective response rate, duration of response, median PFS, overall survival, and safety will also be assessed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bayer Pharma, Pfizer, Roche Bayer, Genentech, Novartis, Pfizer, Roche

Particularités pronostiques, histopathologiques, génétiques et thérapeutiques du carcinome à cellules rénales tubulopapillaire

We reviewed papillary renal cell carcinoma (PRCC) epidemiology, radiological and clinical presentations, and specific features of morphological subtypes focusing on genetic defects, risk of local and metastatic recurrence and frequency of multifocality. The MEDLINE database of the US National Library of Medicine was searched for pertinent studies. According to multivariate analyses, PRCC histology was not retained as a prognostic factor. Reported rates of multifocality in PRCC are 22 to 41% but distinction between histological subtype or hereditary forms are barely detailed. Multifocality frequency is independent of size, stage or grade and is not associated with ipsilateral or controlateral recurrence or death from RCC. Thus, PRCC multifocality is not an argument against nephron-sparing surgery. Antiangionenic therapies are being evaluated for the Metastatic PRCC. According to the literature, specific prognostic features of PRCC remain controversial due to the lack of distinction between different PRCC subtypes. Genomic and cytogenetic characterizations have been used to establish an evolving classification of PRCC subtypes and may be a source of new markers that will eventually enable us to precise prognosis and identify targets for new adjuvant therapies.

Histological Subtype is an Independent Predictor of Outcome for Patients With Renal Cell Carcinoma

There are significant differences in clinicopathological features among renal cell carcinoma histological subtypes but controversy exists regarding the independent impact of histological subtype on patient outcome after nephrectomy. We examined the significance of histological subtype on progression to distant metastasis and cancer specific death after nephrectomy. In a retrospective review of our institutional nephrectomy registry we identified 3,062 patients treated surgically for clear cell, papillary or chromophobe renal cell carcinoma between 1970 and 2003. We identified 2,466 patients (80.5%) with clear cell, 438 (14.3%) with papillary and 158 (5.2%) with chromophobe renal cell carcinoma. There were significant differences in age at surgery, gender, symptoms at presentation, tumor size, stage and grade, tumor necrosis, sarcomatoid differentiation and multifocality among the 3 renal cell carcinoma subtypes (p <0.01 for all). A significant difference in metastasis-free and cancer specific survival existed between patients with clear cell renal cell carcinoma and the 2 other subtypes, although no significant difference in these outcomes was identified between patients with the papillary and chromophobe subtypes. The clear cell renal cell carcinoma subtype remained a significant predictor of metastasis (HR 2.76, 95% CI 2.05-3.73) and cancer specific death (HR 1.77, 95% CI 1.38-2.26, each p <0.001) after multivariate adjustment for the features listed above. Histological subtype is an independent predictor of progression to distant metastasis and cancer specific death in patients with renal cell carcinoma.

Efficacy of sorafenib in treating metastatic non-clear cell renal cell carcinoma

Objective To investigate the efficacy of sorafenib in treating metastatic non-clear cell renal cell carcinoma(RCC).Methods Twenty-one patients with metastatic non-clear cell subtype renal cell carcinoma were treated with sorafenib.Thirteen cases were male,8 were female,with a median age of 45 years(25-76 years).Metastasis occurred in 12 cases after radical nephrectomy,and the other 9 cases received cytoreductive surgery.Pathological diagnosis showed 15 papillary RCCs,1 chromophobe RCC,and 5 unclassified RCCs.The metastatic lesions were located at lung,lymph node,adrenal gland,bone,liver,and thyroid gland.The patients were given the treatment of sorafenib 400 mg bid,or sorafenib 400 mg bid in combination with interferon-α 3 MIU,IH.5 days per week,and the median time of treatment was 8 months (2-21 months).Results Three cases (14.3%)with 1 papillary RCC,1 chromophobe RCC,and 1 unclassified RCC reached partial remission(PR) and 13 cases (61.9%) maintained stable disease (SD) for more than 12 weeks.And the rest 5 cases(23.8%) progressed(PD).To Jul 2009,13 cases progressed and the median progression free survival was 7 months(0-21 months).Conclusions Sorafenib has definitive efficacy in metastatic papillary RCC,chromophobe RCC,and unclassified RCC.Metastatic lesions in lungs and Lymph nodes might be more sensitive to sorafenib. Key words: Carcinoma,renal cell; Non-clear cell; Neoplasm metastasis; Sorafenib

Prognostic Factors of Papillary Renal Cell Carcinoma: Results From a Multi-Institutional Series After Pathological Review

We examined papillary renal cell carcinoma prognostic variables and validated the 2002 UICC TNM staging system in a multicenter analysis. From 10 urological institutions in Germany followup data were collected on a total of 675 patients with papillary renal cell carcinoma. Central pathological review was done to validate external histopathological diagnoses. The Kaplan-Meier method was used to derive cumulative cancer specific and overall survival, and the log rank test was used to compare the curves of 2 or more groups. For multivariate analysis of prognostic factors Cox regression analysis was done. All proportional hazard assumptions were systemically verified using the Grambsch-Therneau test. Cancer specific survival was significantly related to TNM stage and histological grading on univariate and multivariate analyses. Five-year cancer specific survival in pT1b cases was significantly shorter than in pT1a cases (90.0% vs 98.3%, p = 0.017). No significant difference was found between pT1b and pT2 tumors. Patients with pT3 or greater disease were at high risk for metastasis (50.6%) while metastatic disease associated with pT2 or less tumors occurred in 7.8% (p <0.0001). After metastatic disease was present the prognosis was poor with 7.2% 5-year cancer specific survival. Age was associated with poor prognosis in the subgroup with pT3 or greater tumors on univariate analysis (p = 0.026) but not on multivariate analysis. In its current form the 2002 UICC TNM staging system is not applicable to papillary renal cell carcinoma. Clinical and radiological followup should be offered at frequent intervals to patients with venous thrombus and/or locally advanced disease. The role of age remains unclear but should not be underestimated in risk stratification after surgery.

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma

Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies. Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany. Median follow-up was 20 (range 1-114) months and median age at time of diagnosis was 62 (range 24-85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3-143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-alpha +/- interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 +/- 4.3 months 95% CI 4.5-21.5 (n = 42) months in patients without surgical approach. Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.

Metastatic Versus Primary Oncocytic Papillary Adenocarcinoma of the Endometrium: A Report of a Case and Review of the Literature

We report a case of an oncocytic papillary adenocarcinoma of the endometrium in an 89-year-old female with vaginal bleeding. Imaging studies revealed lesions in the uterus, kidneys, pancreas, gluteus, and an enlarged portacaval lymph node. Diagnostic workup included an endometrial biopsy which showed malignant, oncocytic cells in a predominantly papillary pattern. These cells stained positive for epithelial markers (pan-cytokeratin, CK7, epithelial membrane antigen) and weakly for estrogen receptor. The cells were negative for cytokeratin 903, CAM 5.2, progesterone receptor, CD10, RCC Marker, CA-125, c-kit, and vimentin. Consultation with experts in Gynecologic and Genitourinary pathology returned a diagnosis of "adenocarcinoma compatible with metastatic renal cell carcinoma"--an intriguing possibility worthy of further exploration. To our knowledge, there are no reports in the literature of metastatic oncocytic papillary renal cell carcinoma to the endometrium. The clinical and pathologic features of oncocytic papillary endometrial lesions, including primary and metastatic processes, are reviewed.

Recent advances in the systemic treatment of metastatic papillary renal cancer

Renal cell carcinoma (RCC) encompasses a heterogeneous group of histological subtypes, of which clear cell RCC (CCRCC) is the most common, comprising more than 70% of all cases. Papillary RCC (PRCC) is the next most common, comprising 10–15% of cases. PRCC is refractory to chemotherapy, immunotherapy and hormonal therapy. Recent improvements in our understanding of the molecular biology of CCRCC have identified multiple pathways associated with the development of this cancer. This has led to drug development targeting these pathways, including the small molecule tyrosine kinase inhibitors sunitinib and sorafenib, the monoclonal antibody bevacizumab and the mTOR inhibitor temsirolimus. These drugs have shown significant clinical benefits in randomized trials of advanced CCRCC and have become the standard of care for most patients. However, since these trials were, on the whole, restricted to patients with clear cell histology, their efficacy in patients with non-clear cell RCC, and particularly PRCC, is unclear. This review will focus on the activity of these targeted agents in the treatment of metastatic PRCC.

A unique case of spontaneous regression of metastatic papillary renal cell carcinoma: a case report

Spontaneous regression of cancer is a rare, but well documented, phenomenon. We present a unique case of an 82 year old Chinese male who experienced spontaneous regression of histologically-verified metastatic type II papillary renal cell carcinoma in the absence of intervening systemic therapy or surgery. This is the first reported case of spontaneous regression of papillary renal cell carcinoma. The mechanism of spontaneous regression remains unknown, and represents a challenge for existing oncology paradigms.

Phase II Trial of Carboplatin and Paclitaxel in Papillary Renal Cell Carcinoma

Background Cytotoxic chemotherapy has not been well investigated in non–clear-cell renal cell carcinoma (RCC). A phase II study was thus conducted to assess the efficacy of carboplatin and paclitaxel in such patients. Patients and Methods Patients were treated with carboplatin (area under the curve of 6) and paclitaxel 225 mg/m 2 every 21 days and assessed for measurable disease response every 2 cycles. An initial 20 patients were planned to be enrolled to rule out a null hypothesized 15% response rate. Results Seventeen patients were enrolled, of which 16 patients had papillary and 1 had collecting duct histology. The patient with collecting duct histology had a complete response, but no responses were observed in patients with papillary histology and the trial was thus terminated early. Toxicities were as expected for the carboplatin and paclitaxel regimen. Conclusion Carboplatin and paclitaxel is not an active regimen in patients with metastatic papillary RCC. Future studies should explore the role of this or similar regimens in collecting duct carcinoma.

Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma

Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma

A case of port-site recurrence and locoregional metastasis after laparoscopic partial nephrectomy

A 63-year-old man underwent hand-assisted laparoscopic partial nephrectomy for a 4.5 cm right renal mass, pathologically confirmed as type 2 papillary renal cell carcinoma (RCC). Two years later he was referred to a specialist oncology center after routine follow-up raised suspicion for metastatic disease. Physical examination, CT, PET, laboratory analysis of blood and stool samples, fine needle aspiration of the hand-assist site, and colonoscopy with biopsy. Locoregional metastatic papillary RCC with port-site metastasis. The patient underwent excision of his port-site and intra-abdominal recurrences, right hemicolectomy and cholecystectomy. Pathologic examination revealed metastatic papillary RCC at all sites. After a disease-free interval of 12 months, the patient was found to have radiographic evidence of recurrent disease in the liver and peritoneum.

Metastatic type-2 papillary renal cell carcinoma responded to interleukin-2 therapy: case report

This report documents a case of metastatic papillary renal cell carcinoma (PRCC) which successfully responded to interleukin-2 (IL-2) therapy. A 59-year-old male presented with a left renal mass measuring 3.0 cm in diameter and a right adrenal mass measuring 5.0 cm in diameter. He underwent a left partial nephrectomy and a right adrenalectomy. The histological findings revealed pT1bN1M1 type-2 PRCC and metastatic renal cell carcinoma in the right adrenal gland. The patient was given interferon-alpha (IFN-alpha) after the operation for 3 months. A CT scan revealed a metastatic nodule measuring 6.0 cm in diameter near the surface of the liver at 4 months after the operation. The patient was given interleukin-2 (IL-2), 7 x 10(5) units/day intravenously, for 3 days per week. A CT scan revealed this hepatic nodule to have decreased in size from 6.0 to 4.0 cm after 4 months of IL-2 therapy. However, a new metastatic nodule measuring 6.0 cm in diameter was found which came in contact with the spleen. Next, the patient was given an increased dose of IL-2 from 7 x 10(5) to 1.4 x 10(6) units/day intravenously, for 3 days per week. At 9 months of follow-up after the dose escalation, a CT scan revealed a dramatic decrease in the size of these two metastatic nodules to 1.5 and 0.5 cm, respectively. This is a very rare case in that it represents a type-2 PRCC which dramatically responded to low-dose IL-2 therapy.

Papillary renal cell carcinoma: clinicopathological characteristics in 40 patients

Two different subtypes of papillary renal cell carcinoma (PRCC) have so far been identified, type-1 with small cells and pale cytoplasm and type-2 with large cells and eosinophilic cytoplasm. It has generally been accepted that type-1 tumors have favorable features in comparison with type-2 tumors, suggesting that these subtypes could be different clinicopathological entities, and, as a result, that the subtypes need to be characterized. Forty cases of PRCCs were reviewed, with special attention to the distinct clinicopathological difference and the response to cytokine therapy. Thirty-five cases of PRCC diagnosed between January 1997 and August 2007 were reviewed. PRCCs were classified according to the criteria of Delahunt and Eble. Of these 40 patients, 20 and 20 were diagnosed to be type-1 and type-2 PRCCs, respectively. No lymphatic or vascular invasion or distant metastasis were observed in patients with type-1 PRCC. The nuclear grade in all type-1 PRCCs was low grade. The nuclear grade (P <or= 0.01) and the positive rate of vascular invasion (P <or= 0.05) was significantly higher in type-2 than in type-1 PRCCs. Distant metastasis was detected preoperatively in three patients with type-2 PRCC. One patient with metastatic type-2 PRCCs demonstrated a response to IL-2 therapy. PRCCs include two distinct morphological types of tumor and type-2 PRCCs tends to have unfavorable features in comparison with type-1 PRCCs. These results support the clinical basis for the need to perform morphological subtyping of PRCCs when clinically evaluating such patients.

Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma

Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non-clear cell histologies has not been evaluated. Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival. Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two patients treated with sorafenib and one treated with sunitinib), and PFS was 10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated patients (P < .001). Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC. Additional prospective trials with these agents in non-clear cell RCC will further clarify their use in the future.

Treatment outcome for metastatic papillary and chromophobe renal cell carcinoma (RCC) patients treated with tyrosine-kinase inhibitors (TKIs) sunitinib and sorafenib

5037 Background: Sunitinib (SUNI) and sorafenib (SORAF) are novel TKIs that have shown significant clinical activity in metastatic clear-cell RCC. Papillary (PAP) and chromophobe (CHRM) histologies represent the majority non-clear-cell RCC. The activity of SUNI and SORAF in non-clear cell histologies has not been evaluated. Methods: Clinical features at study entry and treatment outcomes were evaluated in all patients (pts) with metastatic PAP and CHRM RCC who received either SUNI or SORAF as their initial TKI treatment at one of five different cancer centers in France and USA between 2002 and 2006. Descriptive statistics were used to evaluate the collected data. Overall Response rate (ORR) was investigator-assessed per RECIST criteria. Fisher’s exact test was used for categorical variables and the Kaplan-Meier method was used to estimate survival (Overall Survival (OS) and progression-free survival (PFS)). Results: Median age for the 53 patients was 59 years and 64% were male. The number of patients with PAP and CHRM histologies were 41 (77%) and 12 (23%), respectively. Nephrectomy was performed in 87% of patients and 33/53 (62%) of pts were previously treated (26/33, 79%, with cytokines). ORR, PFS and OS for the entire cohort were 10%, 8.9 months (m) and 12.2 m, respectively. Twenty (38%) and 33 (62%) pts were treated with SUNI and SORAF, respectively. 3/12 (25%) of CHRM pts had an ORR vs. 2/41(4.8%) with PAP histology (P=0.07). PFS for CHRM pts was 9.3 m compared to 6.6 m for PAP pts (p=0.07). OS was not different across histologies and type of TKI received. SUNI treated pts had an ORR of 15% and PFS of 11.9 m compared to 6% (p=0.3) and 5.5 m for SORAF pts (p=0.002), respectively. Other factors found to be associated with shorter PFS include ECOG PS &gt;0 (p=0.03) and hemoglobin&lt; normal (p=0.02). Conclusions: TKI may have activity in metastatic CHRM RCC, similar to what is seen in clear-cell histology. Minimal activity however is noted in PAP RCC, justifying continued investigations of novel agents in this histology. No significant financial relationships to disclose.

Treatment of metastatic papillary renal cell carcinoma with immunochemotherapy with interleukin-2, interferon-alpha and 5- fluorouracil

15644 Background: Combined immunochemotherapy with interleukin-2 (IL-2), interferon-alpha (IFN-a) and 5-fluorouracil (5-FU) is an established first-line therapy for metastatic renal cell carcinoma (RCC). However, data on histologic parameters predictive of clinical benefit are rare. Methods: Treatment courses of 164 patients consisted of IFN-a at 9 x 106 IU on day 1 of weeks 1 and 4 and days 1, 3, 5 of weeks 2 and 3; and at 18 x 106 IU on days 1, 3, 5 of weeks 5–8. Interleukin-2 was administrated at 18 x 106 IU twice daily on days 3–5 of weeks 1 and 4; and at 9 x 106 IU on days 1, 3, 5 of weeks 2 and 3. Additionally, patients received 5-FU at 750 mg m-2 on day 1 of weeks 5–8. In 153 patients, radical nephrectomy had revealed 22 cases of papillary RCC (pRCC, 13.4%) and 131 cases of clear cell RCC (ccRCC, 79.9%). In the remaining 11 (6.7%) their disease was inoperable. The overall response rates were evaluated according to WHO criteria. Results: For ccRCC and inoperable disease, responses of 34.4% and 27.3% after one cycle and 28.8% and 16.7% after two cycles, respectively, were noted. In contrast, no patient with pRCC showed any response after two cycles of combined immunochemotherapy. Conclusions: No objective response was seen in patients with pRCC. Hence, immunotherapeutic agents must be questioned in this histologic subtype. No significant financial relationships to disclose.

A phase II study of the c-Met RTK inhibitor XL880 in patients (pts) with papillary renal-cell carcinoma (PRC)

15601 Background: XL880 is a novel inhibitor of receptor tyrosine kinases targeting MET and VEGFR2/KDR. (IC 50 for MET 0.4nM and KDR 0.8 nM). PRC is a rare (10–15%) subtype of kidney cancer which is notoriously resistant to systemic treatment. The familial form of PRC is associated with germline activating mutations of MET, while amplification and overexpression of MET is seen in the sporadic form. In an ongoing phase I dose escalation study of XL880 in forty patients with advanced solid tumors, five partial responses (PRs) were noted in 3 of 4 treated patients with PRC, and in two pts with thyroid cancer. The MTD in this study was 3.6 mg/kg of XL880 administered orally daily for 5 consecutive days every 2 weeks. Methods: In this phase 2 study, XL880 is administered orally as a single agent at a dose of 240 mg on days 1–5 of each 14 day cycle. Previously untreated pts with a histologic diagnosis of metastatic PRC are eligible and are stratified based on the presence or absence of MET germline mutations. Planned enrollment is 15 evaluable pts in each stratum. Inclusion criteria also include ECOG performance status &lt; 3 and absence of brain metastases. Tumor response is assessed every 8 weeks by RECIST criteria. Archival primary tumor and lymph node metastasis were collected for pharmacodynamic assessments. Results: To date, 6 pts have been enrolled and received XL880. Five pts have tested negative for MET germline mutations; results for one pt are pending. Of 3 pts with at least one post baseline tumor assessment, 1 pt has demonstrated a PR and two pts have demonstrated stable disease &gt; 3 months, one of whom has improvement in bone scan and bone pain. Hypertension has been reported in 2 pts who responded to anti- hypertensive treatment. Two SAEs have been reported as unrelated; pulmonary embolism and intratumoral hemorrhage. MET expression was detected in untreated primary and metastatic tumor. Reduction in Ki67, and an increase in TUNEL labeling were observed in the post treatment sample. Conclusions: XL880 is the 1st orally available small molecule inhibitor of MET to enter the clinic and appears to be generally well tolerated. Anti-tumor activity has been observed and XL880 may represent an active treatment option for pts with PRC. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.