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​Applying the Latest Evidence to Improve Care for Patients with HR+/HER2- Metastatic Breast Cancer

Expiration date: December 13, 2019

On November 26, 2018, the Food and Drug Administration granted accelerated approval to larotrectinib (VITRAKVI, Loxo Oncology Inc. and Bayer) for adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment.

This is the second tissue-agnostic FDA approval for the treatment of cancer.

Approval was based on data from three multicenter, open-label, single-arm clinical trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431). Identification of positive NTRK gene fusion status was prospectively determined in local laboratories using next generation sequencing (NGS) or fluorescence in situ hybridization (FISH). NTRK gene fusions were inferred in three pediatric patients with infantile fibrosarcoma who had a documented ETV6 translocation by FISH. The major efficacy outcome measures were overall response rate (ORR) and response duration, as determined by a blinded independent review committee according to RECIST 1.1.

​Efficacy was evaluated in the first 55 patients with unresectable or metastatic solid tumors harboring an NTRK gene fusion enrolled across the three trials.  All patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease. Twelve patients were less than 18 years of age. A total of 12 cancer types were represented, with the most common being salivary gland tumors (22%), soft tissue sarcoma (20%), infantile fibrosarcoma (13%), and thyroid cancer (9%).

ORR was 75% (95% CI: 61%, 85%), including 22% complete responses and 53% partial responses. At the time of database lock, median duration of response had not been reached. Response duration was 6 months or longer for 73%, 9 months or longer for 63%, and 12 months or longer for 39% of patients. 


Read more here: 
https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626720.htm

On Sept. 28, 2018, the Food and Drug Administration approved cemiplimab-rwlc (LIBTAYO, Regeneron Pharmaceuticals Inc.) for patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation.

Approval was based on clinically meaningful and durable objective response rates (ORR) observed in patients with advanced CSCC who were treated with cemiplimab-rwlc in two clinical trials: R2810-ONC-1423, an open-label, multi-center, dose-finding trial with expansion cohorts in patients with various advanced solid tumors; and R2810-ONC-1540, an open-label, multi-center, non-randomized, multicohort trial in patients with metastatic or locally advanced CSCC regardless of prior treatment, for whom surgery or radiation was not recommended.

ORR was assessed by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for patients with metastatic CSCC. A composite response assessment incorporating clinical response criteria using digital photography and RECIST 1.1 was used for those with locally advanced CSCC.

More information here.

FDA  updated the prescribing information for Keytruda (pembrolizumab) and Tecentriq (atezolizumab) to require the use of an FDA-approved companion diagnostic test to determine PD-L1 levels in tumor tissue from patients with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible. FDA approved two different companion diagnostic tests, one for use with Keytruda and one for use with Tecentriq, More Information. August 16, 2018.

On August 16, 2018, the FDA approved the Dako PD-L1 IHC 22C3 PharmDx Assay (Dako North America, Inc.) as a companion diagnostic to select patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Keytruda. The 22C3 assay determines PD-L1 expression by using a combined positive score (CPS) assessing PD-L1 staining in tumor and immune cells.

On July 2, 2018, the FDA approved the Ventana PD-L1 (SP142) Assay® (Ventana Medical Systems, Inc.) as a companion diagnostic test to select patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Tecentriq. The SP142 assay determines PD L1 expression in immune cells. 

Read more about the updated indications here.

FDA  approved ivosidenib (Tibsovo, Agios Pharmaceuticals, Inc.) for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.  More Information.  July 20, 2018

A free online CME activity is now available on Univadis:

​Improving Metastatic Colorectal Cancer (mCRC) Care in Community Cancer Centers

This CME activity is jointly provided by American Academy of CME, Inc. and Q Synthesis LLC.

CME credit for this activity will expire on April 20, 2019.

​The clinical management of patients with metastatic colorectal cancer (mCRC) continues to evolve as advances in research lead to new approaches in molecular biomarker testing and the application of treatment plans that are tailored for each patient. The goal of this program is to educate and enable members of the cancer care team to apply the latest guidelines and evidence when managing patients with mCRC. 

​Roche and Foundation Medicine, Inc. announced they have entered into a definitive merger agreement for Roche to acquire the outstanding shares of FMI’s common stock not already owned by Roche and its affiliates. This corresponds to a total transaction value of US$ 2.4 billion. 

Daniel O’Day, CEO Roche Pharmaceuticals, said, “This is important to our personalised healthcare strategy as we believe molecular insights and the broad availability of high quality comprehensive genomic profiling are key enablers for the development of, and access to, new cancer treatments. We will preserve FMI’s autonomy while supporting them in accelerating their progress.”

Foundation Medicine, based in Cambridge, Massachusetts, is a market leading molecular information company dedicated to a transformation in cancer care, where each patient’s treatment is informed by a deep understanding of the molecular changes that contribute to their disease. Their services include a full suite of comprehensive genomic profiling (CGP) assays to identify the molecular alterations in a patient's cancer and match them with relevant targeted therapies, immunotherapies and clinical trials.

“Foundation Medicine and Roche share the philosophy that every cancer patient should have access to personalized care informed by validated molecular information. Joining forces with Roche as an independent operating company allows Foundation Medicine to continue its collaboration with Roche, as well as our biopharma partners, to drive ubiquitous access to CGP testing and innovative data services,” said Troy Cox, Chief Executive Officer for Foundation Medicine.

On May 1, 2018, the FDA approved tisagenlecleucel (KYMRIAH, Novartis Pharmaceuticals Corp.) a CD19-directed genetically modified autologous T-cell immunotherapy, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. 

​Approval was based on a single-arm, open-label, multi-center, phase 2 trial (JULIET, NCT02445248) in adults with relapsed or refractory DLBCL and DLBCL after transformation from follicular lymphoma. Eligible patients must have been treated with at least two prior lines of therapy, including an anthracycline and rituximab, or relapsed following autologous hematopoietic stem cell transplant. Patients received a single infusion of tisagenlecleucel following completion of lymphodepleting chemotherapy.
The overall response rate (ORR) as assessed by an independent review committee for the 68 evaluable patients was 50% (95% CI: 37.6, 62.4) with a complete response (CR) rate of 32% (95% CI: 21.5, 44.8). With a median follow-up time of 9.4 months, the duration of response (DOR) was longer in patients with a best overall response of CR, as compared to a best overall response of partial response (PR). Among patients achieving CR, the estimated median DOR was not reached (95% CI: 10.0 months, not estimable [NE]). The estimated median response duration among patients in PR was 3.4 months (95% CI: 1.0, NE).

The most common adverse reactions (incidence >20%) in patients on the trial were cytokine release syndrome (CRS), infections-pathogen unspecified, pyrexia, diarrhea, nausea, fatigue, hypotension, edema, and headache. Because of the serious risks of CRS and neurologic toxicities, FDA approved tisagenlecleucel with a Risk Evaluation and Mitigation Strategy.

FDA approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.  More Information.  April 19, 2018

Today, the FDA approved nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb Co.) in combination for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma. 

​On April 16, 2018, the Food and Drug Administration granted approvals to nivolumab and ipilimumab (Opdivo and Yervoy, Bristol-Myers Squibb Co.) in combination for the treatment of intermediate or poor risk, previously untreated advanced renal cell carcinoma.

The approvals were based on CheckMate 214 (NCT02231749), a randomized open-label trial. Patients with previously untreated advanced RCC received nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for 4 doses followed by nivolumab monotherapy (3 mg/kg) every 2 weeks, or sunitinib 50 mg daily for 4 weeks followed by 2 weeks off every cycle.

Efficacy was evaluated in intermediate or poor-risk patients (n=847). The trial demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) for patients receiving the combination (n=425) compared with those receiving sunitinib (n=422). Estimated median OS was not estimable in the combination arm compared with 25.9 months in the sunitinib arm (hazard ratio 0.63, 95% CI: 0.44, 0.89; p<0.0001). The ORR was 41.6% (95% CI: 36.9, 46.5) for the combination versus 26.5% (95% CI: 22.4, 31) in the sunitinib arm (p<0.0001). The efficacy of the combination in patients with previously untreated renal cell carcinoma with favorable-risk disease was not established.

The most common adverse reactions (reported in at least 20% of patients treated with the combination) were fatigue, rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, and decreased appetite.

The recommended schedule and dose for this combination is nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, on the same day every 3 weeks for 4 doses, then nivolumab, 240 mg, every 2 weeks or 480 mg every 4 weeks.