Virginia Powers

Inhibition of CDK4/6 results in improvements in progression-free survival (PFS) in women with estrogen receptor (ER)-positive HER2-negative metastatic breast cancer whether it is endocrine sensitive or resistant, according to an overview presented at the 25th St. Gallen Breast Cancer Conference.

Cancer progression is earmarked by loss of control over the cell cycle. One of the critical elements of cell cycle control is the estrogen-dependent cyclin D1-CDK 4/6-retinoblastoma (Rb) pathway, which controls the checkpoint for entry into the S-Phase, according to Sibylle Loibl, MD, PhD, co-chair of the German Breast Group and associate professor at the University of Frankfurt in Frankfurt, Germany.

&ldquo;CDK4/6 inhibition is the most well-advanced cell cycle targeting strategy to date,&rdquo; commented Loibl. &ldquo;I called my talk &lsquo;targetable pathways on the horizon&rsquo;, but some CDK 4/6 inhibitors are already at the horizon, since palbociclib and ribociclib have already been approved,&rdquo; she said. A third selective CDK4/6 inhibitor, abemaciclib (LY2835219) is in clinical development.

Palbociclib (Ibrance) was the first CDK4/6 inhibitor to be tested in early stage breast cancer. It had been reported to inhibit proliferation in luminal ER-positive and HER-negative amplified human breast cancer cell lines in vitro, but is effective only where functional retinoblastoma protein (Rb) is present; sensitive cells express high levels of Rb and cyclin D1, and low levels of CDKN2A

Clinical data from the phase II, randomized PALOMA 1/TRIO 18 trial of palbociclib plus letrozole showed that the addition of palbociclib improved progression-free survival (PFS) over letrozole in postmenopausal women with ER-positive, HER2- negative advanced breast cancer. Median PFS with palbociclib/letrozole was 26.1 versus 5.7 months with letrozole (

<.0001) in cohort 1 of women with ER-positive, HER2-negative breast cancer and 18.1 versus 11.1 months (

= .0046) in the respective treatment arms in cohort 2, which included women with ER-positive HER2-negative disease who also had amplification of CCND1, loss of p16, or both.

Findings from the PALOMA 3 trial supported the FDA accelerated approval of palbociclib for the treatment of ER-positive HER2-negative metastatic breast cancer. PALOMA 3 demonstrated median PFS of 9.5 months with palbociclib/fulvestrant versus 4.6 months with placebo/fulvestrant (

&ldquo;The beauty of PALOMA 3 is that it also included premenopausal women,&rdquo; said Loibl. In this cohort, median PFS with palbociclib/fulvestrant was 9.5 versus 5.6 months (

= 0.013) compared to 9.9 months versus 3.9 months (

<.0001) with the respective treatments in the postmenopausal cohort.

When the PALOMA 3 data were reevaluated according to

mutation status, the analysis showed the PFS benefit with palbociclib was retained regardless of

Ribociclib was granted FDA approval earlier this week based upon findings from the phase III MONALEESA 2 trial which demonstrated a 44% implement in PFS with ribociclib/letrozole over placebo/letrozole (

= .00001) in postmenopausal women with previously untreated ER-positive HER2-negative metastatic breast cancer. Adjuvant ribociclib (Kisqali) also demonstrated a mean decrease in Ki-67 protein from baseline of 96% versus 69% with letrozole.

Abemaciclib is the third CDK4/Cyclin D1 inhibitor in the pipeline that has the distinction of being less potent that palbociclib or ribociclib, which may have the important clinical implication of reduced toxicity. Thus far, phase I trial data has demonstrated that neutropenia is not a dose limiting toxicity, allowing for continuous dosing.

Heavily pretreated patients with ER-positive HER2-negative metastatic breast cancer were treated with abemaciclib as monotherapy and showed a 19.7% overall response rate consisting of all partial response and stable disease lasting more than 6 months in 42.2% of patients. Median PFS was 6.0 months. The median time to response was 3.7 months, median overall survival was 17.7 months, and the median duration of response was 8.6 months.

Abemaciclib is being further studied in combination with anastrozole in the neoMONARCH trial, wherein an expression change in Ki-67 levels of over 80% from baseline by week 2 at two dose levels compared to a 21% decrease with anastrozole monotherapy. The neoMONARCH study met the boundary for statistical significance (P <.01) at the interim analysis.

Loibl outlined further studies of CDK 4/6 pathway inhibitors such as the NeoPalAna, which is evaluating the ability of palbociclib to achieve complete cell cycle arrest (primary endpoint), defined as Ki-67 &le; 2.7%, and also by luminal A and B subtypes.

The PADMA trial is investigating palbociclib plus endocrine therapy compared to physician&rsquo;s choice of chemotherapy with and without endocrine therapy. The primary endpoint of PADMA is time to treatment failure and, to date, 160 women with HER+ HER2-negative metastatic breast cancer have been enrolled. The PATINA trial will investigate palbociclib plus endocrine therapy plus physicians choice of trastuzumab with or without pertuzumab compared to trastuzumab plus pertuzumab and endocrine therapy.

The PENELOPE study plans to enroll 1100 patients with HR-positive HER2-negative breast cancer to test palbociclib versus placebo both in combination with neoadjuvant chemotherapy followed by surgery with and without radiotherapy. &ldquo;No biomarkers have been identified for patient selection have been identified and it is very clear that patient selection strategies will be important in determining the optimal benefit from CDK4/6 inhibition,&rdquo; Loibl concluded.

Finn RS, Dreing J, Conklin D, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro.

Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

2015;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3.

Loibl S, Turner NC, Ro J, et al. Palbociclib (PAL) in combination with fulvestrant (F) in pre-/peri-menopausal (PreM) women with metastatic breast cancer (MBC) and prior progression on endocrine therapy-results from Paloma-3. Abstract presented at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL. Abstract 524.

Goetz MP, Beeram M, Beck T, et al. Abemaciclib, an inhibitor of CDK4 and CDK6, combined with endocrine and HER2-targeted therapies for women with metastatic breast cancer. Abstract presented at: 38th Annual San Antonio Breast Cancer Symposium; December 8-12; San Antonio, TX. Abstract P4-13-25.

Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH1: Results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+?HER2- breast cancer, after chemotherapy for advanced disease. Abstract presented at: 2016 ASCO Annual Meeting; June 3-7, 2016; Chicago, IL. Abstract 510.

Hurvitz S, Martin M, Abad MF, et al. Biological and clinical effects of abemaciclib in a phase 2 neoadjuvant study for postmenopausal patients with HR+, HER2- breast cancer. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10; San Antonio, TX. Abstract S4-06.

Ma CX X, Gao F, Northfelt D, et al. A phase II trial of neoadjuvant palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with anastrozole for clinical stage 2 or 3 estrogen receptor positive HER2 negative (ER+HER2-) breast cancer (BC). Abstract presented at: 2015 San Antonio Breast Cancer Symposium; Demeber 8-12, 2015; San Antonio, TX. Abstract S6-05.

Loibl S. Targeting the CDK4/6 pathway from research to clinic. Presentation presented at: 15th St. Gallen International Breast Cancer Conference; March 15-18, 2017; Vienna, Austria.

Articles

Inhibition of CDK4/6 results in improvements in progression-free survival in women with estrogen receptor ER-positive HER2-negative metastatic breast cancer whether it is endocrine sensitive or resistant.

An Expert's Overview of CDK4/6 Inhibitors for HR+/HER2- Metastatic Breast Cancer

Several subtypes of difficult-to-treat sarcomas may respond to treatment with PD-1 pathway inhibiting immunotherapies, according to findings of an immunohistochemistry (IHC) analysis of a large patient population presented at the 2017 European Cancer Congress in Amsterdam

Researchers evaluated the expression and clinical association of the key molecules in the PD-1 pathway and its primary ligand, PD-L1, on tumors and on cells in the tumor microenvironment of pediatric and young adult patients with sarcoma. The investigators also looked for the presence of CD8 expression on the tumors and on cells in the microenvironment, which has been associated with superior survival for patients with localized osteosarcoma

PD-1/PD-L1 expression is only just beginning to garner attention in sarcoma subtypes, says Anke van Erp, PhD, MSc, of the Radboud University Medical Center in Nijmegen, the Netherlands.

&ldquo;The interaction of PD-1 and PD-L1 results in negative regulation of T-cell activity, which can be blocked by PD-1 antibodies,&rdquo; she explained.

With her colleagues, van Erp used IHC to evaluate protein expression on primary tumor samples of 217 patients who were stratified by age at diagnosis into cohorts of <18 years and &ge;18 years. They evaluated formalin-fixed paraffin-embedded tumor sections of 52 primary osteosarcoma samples, 22 Ewing sarcoma (ES), 42 alveolar rhabdomyosarcoma (ARMS), 80 embryonal RMS (ERMS), 29 synovial sarcoma (SyS), and 9 desmoplastic small round cell tumor (DSRCT) patient samples by IHC for the expression of PD-1 (using clone MRQ-22), PD-L1 (clone E1L3N), and CD8+ cells (clone C8/144B). Samples having fewer than 10% positively staining cells for each marker were classified as negative and positive if samples showed 10% to 50% of stained cells. Samples with &ge;50% stained cells for PD-1, PD-L1 or CD8 were determined highly positive for the specific marker.

The investigators found that cell surface PD-L1 expression by tumor cells and immune infiltrates varied significantly by tumor subtype and was most abundant in DSRCT, where it was expressed by 100% of tumor cells. PD-1 tumor cell expression was expressed on 19% of osteosarcoma and ES tumor cells but not on the other subtypes investigated in this series. PD-1 was expressed on 17% of infiltrating lymphocytes in SyS and at levels of &le;6% on the lymphocytes of osteosarcoma, ARMS, and ERMS samples but not by the other subtypes. PD-L1 expression was highest (18%) in ARMS, followed by 16% on ERMS, 13% DSRCT, and 8% in osteosarcoma samples. No PD-L1 expression was seen in SyS or ES samples.

CD8+ expressing cells were found in all subtypes, including in 76% of DSRCT samples, 66% of osteosarcoma, 43% SyS, 41% ES, and in 39% of ERMS samples. In the DSRCT subtype, 13% of the samples had all 3 markers compared to osteosarcoma wherein just 2% of the specimens showed this same staining.

When the investigators explored the association of expression with the clinical outcome of overall survival (OS) at a follow-up of 100 months in sarcoma patients overall, they found no significant association between OS and expression of PD-1, PD-L1, or CD8.

However, they did find a strong correlation in the ARMS subtype where PD-L1 tumor expression significantly correlated with better OS (

= .007) in patients compared with patients with tumors expressing low or no PD-L1.

The investigators also identified ES patients aged &ge;18 years with tumors expressing PD-1 as a cohort that was associated with poorer EFS (

Further evaluation of PD-1, PD-L1, and CD8+ expression in patients with sarcoma and metastatic disease is planned. &ldquo;This research was limited by small samples of these relatively rare sarcoma subtypes but we were able to demonstrate that PD-1and PD-L1 expression and clinical association in sarcoma is subtype dependent; PD-L1 expression in ARMS correlates with better OS and EFS and PD-1 expression on ES and DSRCT tumor cells correlates with worse EFS,&rdquo; van Erp summarized.

Van Erp noted that this was the first time that high levels of PD-1 expression, either alone or in combination with PD-L1, were demonstrated on the tumors of DSRCT patients, who also showed co-expression of CD8+ cells. Co-chair of the session, Stefan Sleijfer of the Erasmus Medical Center in the Netherlands agreed that the high levels of PD-1, PD-L1, and CD8 expression in DSRCT warrants further investigation into whether PD-1 blockade could have clinical benefit in DSRCT patients.

van Erp A, Versleijen-Jonkers Y, Hillebrandt-Roeffen M, et al. Exploring the potential for PD-1 blockade in sarcoma patients. Presented at: 2017 European Cancer Congress; January 27-30, 2017; Amsterdam, the Netherlands.

Palmerini E, Agostinelli C, Picci P, et al. PD1 and PDL1 expression, tumoral microenvironment (TME) characterization and clinical implication in localized osteosarcoma. Presented at: 2016 ESMO Congress; October 7-10, 2016; Copenhagen, Denmark. Abstract 1399PD.

Several subtypes of difficult-to-treat sarcomas may respond to treatment with PD-1 pathway inhibiting immunotherapies, according to findings of an immunohistochemistry analysis of a large patient population.

Potential Promise for PD-1 Blockade Seen in Sarcoma Subtypes

Patients receiving the same diagnosis, colorectal cancer (CRC) with synchronous peritoneal metastases (PM), were offered different treatments that led to dramatically different outcomes based upon the institution in which they were diagnosed. Findings presented at the 19th European Cancer Congress (ECCO 2017) revealed underutilization of a highly effective treatment, due to a lack of referral.

This study showed that only patients diagnosed at a hyperthermic intraperitoneal chemotherapy (HIPEC) center or an academic teaching hospital were likely to be offered cytoreductive surgery (CRS) and HIPEC treatment. During the 10 years that CRS/HIPEC treatment has been available, randomized controlled trials have demonstrated prolonged survival with the combination treatment as compared with the standard care of conventional surgery and systemic chemotherapy.

With CRS/HIPEC, surgeons remove all visible tumors from the abdominal cavity, which is then bathed with chemotherapy that has been heated to 42 degrees Celsius to kill any remaining cancer cells. Hyperthermia augments the cytotoxicity of chemotherapy, and intraperitoneal installation allows for delivery of much higher doses locally than are possible systemically, while minimizing toxicity, according to Koen P. Rovers, MD, Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.

"HIPEC has demonstrated significant clinical benefit in 25% to 30% of patients with colorectal cancer and peritoneal metastasis, and is a vast improvement on systemic chemotherapy," said Rovers.

Rovers and colleagues used data contained in the Netherlands Cancer Registry, which is a nationwide registry that maintains records on every patient newly diagnosed with cancer in each of the 89 hospitals in the Netherlands. For this study, the investigators used all records for patients diagnosed with CRC and PM, but without concurrent systemic metastases, from 2005 to 2015.

Multivariate logistic regression analysis was done per hospital category (HIPEC center versus non-HIPEC, and academic/teaching hospital versus non-teaching) to devise the odds ratio (OR) for the use of CRS/HIPEC and the hazard ratio (HR) for the risk of death for the patients was calculated by multivariate Cox regression analysis. The analyses were adjusted by patient-related confounding variables, including age, gender, and socioeconomic status, and for tumor-related variables such as T-stage, N-stage, location, histology, and the degree of differentiation.

The study showed that only patients diagnosed with CRC plus PM in a HIPEC center stood a good chance of being offered CRS/HIPEC treatment. Out of the 154 (5%) patients newly diagnosed in a HIPEC center, 33% of patients were referred to this treatment, compared with 13% of the 2507 (94%) patients diagnosed with CRC plus PM in a non-HIPEC center.

This disparity in the use of CRS/HIPEC treatment led to variations in patient outcome: Overall survival (OS) was 14.1 months for patients diagnosed in a HIPEC center compared with OS of 9.6 months for patients diagnosed in a non-HIPEC center (HR 0.82; 95% CI, 0.67-0.99).

The investigators then reviewed the variability within non-HIPEC institutions by categorizing them as high (patients diagnosed = 778 [31%]) versus low frequency (patients diagnosed = 875 [35%]) hospitals per the number of cases, and found OS was 12.6 months in patients diagnosed in a high frequency institution versus 8.1 months in a low frequency hospital (HR = 0.73; 95% CI, 0.66-0.81).

The comparison of OS between academic/teaching hospitals where 17% of patients were referred for CRS/HIPEC versus non-teaching hospitals where 11% of patient were referred for this treatment showed OS was 11.5 versus 8.7 months in patients diagnosed in the respective institutions (HR = 0.87; 95% CI, 0.80-0.95).

&ldquo;Diagnosis of colorectal cancer and synchronous peritoneal metastases in HIPEC centers and academic/teaching hospitals led to a higher likelihood of a patient being referred to and receiving CRS/HIPEC and a lower risk of death compared to patients diagnosed in non-HIPEC centers and non-teaching hospitals,&rdquo; Rovers explained.

&ldquo;Although available, CRS/HIPEC appears to be underutilized in the Netherlands, leading to suboptimal treatment of patients,&rdquo; Rover commented.

Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.

.2011;18(6):1575-1581. doi: 10.1245/s10434-011-1631-5.

Rovers K, Simkens G, Vissers P, et al. Survival of patients with colorectal peritoneal metastases is affected by treatment disparities among hospitals of diagnosis: a nationwide population-based study. Abstract presented at: 19th European Cancer Congress; January 27-30, 2017; Amsterdam, Netherlands.

Patients receiving the same diagnosis, colorectal cancer with synchronous peritoneal metastases (PM), were offered different treatments that led to dramatically different outcomes based upon the institution in which they were diagnosed.

Study Findings Show Highly Effective Colorectal Cancer Treatment is Underutilized

Treatment with the PD-1 inhibitor pembrolizumab (Keytruda) significantly prolonged overall survival (OS) over investigators&rsquo; choice of chemotherapy in patients with recurrent advanced urothelial carcinoma, according to results reported at the 19th European Cancer Congress (ECCO 2017). Findings from the phase III Keynote-045 study support pembrolizumab as a new standard of care for patients with advanced urothelial carcinoma that progressed during or after platinum-base chemotherapy.

Urothelial carcinoma is currently treated in the first-line setting with platinum-based chemotherapy, and there is no standard therapy for recurrent or progressive disease.

At a median follow-up of 14.1 months (range: 9.9-22.1), the median OS with pembrolizumab was 10.3 months (95%CI, 8.0- 11.8) compared with 7.4 months (95%CI, 6.1- 8.3) with standard chemotherapy (HR, 0.723; 95% CI, 0.59-0.91;

<.0022). One-year OS rates were 43.9% with pembrolizumab versus 30.7% with chemotherapy.

The confirmed objective response rate was 21.1% with pembrolizumab compared to 11.4% with chemotherapy (P = .0011). Complete response (CR) was reported for 7% of patients, and partial response (PR) for 14.1% of patients treated with pembrolizumab, compared to a CR in 3.3% and a PR in 8.1% of patients receiving chemotherapy.

&ldquo;Pembrolizumab is the first agent to demonstrate OS improvement compared with chemotherapy in patients with advanced urothelial carcinoma after failure of platinum-based chemotherapy,&rdquo; said Andrea Necchi, Fondazione IRCCS Istituto Nazionale dei Tumori, in Milan, Italy. &ldquo;This is the first immunotherapy to demonstrate OS benefit over an active comparator in urothelial carcinoma.&rdquo;

In the KEYNOTE-045 trial, 270 patients with advanced urothelial carcinoma were randomized after the failure of platinum-based doublet chemotherapy to pembrolizumab at 200&thinsp;mg every 3 weeks for 24 months, and 272 patients to receive the investigator's choice of paclitaxel at 175&thinsp;mg/m

, each administered every 3 weeks. Randomization was stratified by ECOG performance status (0/1 versus 2), liver metastases (yes versus no), hemoglobin level (<10 versus &ge;10&thinsp;g/dL), and the time from last chemotherapy (<3 versus &ge;3&thinsp;months). The median patient age was 66 years, and nearly all patients had an ECOG performance status of 0 or 1.

There was no significant difference in progression-free survival (PFS); median PFS was 2.1 months with pembrolizumab compared with 3.3 months with chemotherapy (

&ldquo;The objective response rate was significantly higher, and the response was more durable with pembrolizumab,&rdquo; said Necchi.

For those receiving pembrolizumab, the median time to response was 2.1 months (range: 1.4-6.3) compared with 2.1 months (range: 1.7-4.9) with chemotherapy. The median duration of response (DoR) was not reached (range: 1.6-15.4+) with pembrolizumab, and 4.3 months (range: 1.4-15.4+) with chemotherapy.

A combined positive score was determined in patients with quantifiable PD-L1 expression on tumor and infiltrating immune cells; patients with high PD-L1 expression were described CPS &ge;10.

In the CPS &ge;10 cohort 74 patients received pembrolizumab and 90 patients received chemotherapy. Median OS was 8.0 months versus 5.2 months, and 1-year OS rates were 39.8% with pembrolizumab versus 26.97% with chemotherapy. However, the ORR with pembrolizumab was 21.6% compared with 6.7% with chemotherapy.

&ldquo;Pembrolizumab benefit was observed regardless of PD-L1 expression, &ldquo;Necchi commented.

The KEYNOTE-045 investigators also performed a meta-analysis of OS in studies of second-line immunotherapy for advanced urothelial carcinoma that showed the median OS of 10.30 months demonstrated in this study was greater that the 9.7 months seen with nivolumab in a phase I/II trial

, the 8.74 months with nivolumab in a phase II trial

and the 7.9-month OS shown with atezolizumab in a phase II trial.

The median exposure with pembrolizumab was 3.5 months (range, 0.03-20.0) with pembrolizumab compared to 1.5 months (range, 0.03-14.2) with chemotherapy.

Treatment-related adverse events (TRAEs) were less frequent with pembrolizumab compared with chemotherapy. The rates of all-grade TRAEs were 60.9% and 90.2%, and Grade 3-5 TRAEs occurred in 15% of patients treated with pembrolizumab and 49.9% in patients treated with chemotherapy. TRAEs with pembrolizumab occurring at an incidence of &ge;10% were pruritus (20%), fatigue (10%), nausea (10%), and diarrhea (10%).

Treatment discontinuation due to a TRAE was reported for 15 (5.6%) pembrolizumab patients compared to 28 (11%) of chemotherapy patients. Four deaths due to a TRAE occurred in each arm.

&ldquo;The data from KEYNOTE-047 demonstrated that pembrolizumab treatment resulted in durable overall survival benefit with lower incidence of serious adverse events versus chemotherapy,&rdquo; said Necchi. &ldquo;Pembrolizumab should become the new standard of care for advanced urothelial carcinoma that progressed on or after platinum-based chemotherapy.&rdquo;

The FDA approved pembrolizumab on October 24, 2016, for the treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1, as determined by an FDA-approved test.

Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial.

. 2016;17(11):1590-1598. doi: 10.1016/S1470-2045(16)30496-X.

Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial.

. 2017:pii: S1470-2045(17)30065-7. doi: 10.1016/S1470-2045(17)30065-7.

Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.

. 2016;387(10031):1909-1920. doi: 10.1016/S0140-6736(16)00561-4.

Necchi A, Bellmunt J, de Wit R, et al. Pembrolizumab vs investigator-choice chemotherapy for previously treated advanced urothelial cancer: Phase 3 KEYNOTE-045 study. Abstract presented at: 19th European Cancer Congress; January 27-30, 2017; Amsterdam, Netherlands.

Treatment with the PD-1 inhibitor pembrolizumab significantly prolonged overall survival over investigators&rsquo; choice of chemotherapy in patients with recurrent advanced urothelial carcinoma.

Virginia Powers | Authors

Articles

An Expert's Overview of CDK4/6 Inhibitors for HR+/HER2- Metastatic Breast Cancer

Potential Promise for PD-1 Blockade Seen in Sarcoma Subtypes

Study Findings Show Highly Effective Colorectal Cancer Treatment is Underutilized

Study Results Support Pembrolizumab as Second-Line Standard of Care in Urothelial Carcinoma