pharmacist considerations for new and emerging oral

© 2021 All rights reserved.No part of this report may be reproduced or distributed without the expressed written permission of PTCE.

© 2021 All rights reserved.No part of this report may be reproduced or distributed without the expressed written permission of PTCE.

Pharmacist Considerations for New and Emerging Oral Oncolytics: Optimizing Therapy and Care for Patients Receiving Treatment

Faculty Information

Ashley E. Glode, PharmD, BCOP

Assistant Professor, Department of Clinical Pharmacy

University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

Aurora, Colorado

Some of the original content for this program was developed by:Kirollos S. Hanna, PharmD, BCPS, BCOPOncology Pharmacy ManagerM Health Fairview

Assistant Professor of PharmacyMayo Clinic College of MedicineMaple Grove, Minnesota

Educational Objectives for Pharmacists, Nurses, and Physicians

After completion of this activity, participants will be able to:

• Identify new and emerging oral oncolytics based on pharmacologic properties and mechanisms of action

• Evaluate indications of approved oral oncolytics and their places in treatment guidelines and potential indications and roles in therapy of pipeline oral oncolytics

• Distinguish effective strategies for educating patients about the proper use of oral oncolytics and management of adverse effects

Educational Objectives for Pharmacy TechniciansAfter completion of this activity, participants will be able to:

• Recall mechanisms of action of new and emerging oral oncolytics

• Review indications of approved oral oncolytics and potential indications of pipeline agents

• Detail effective strategies to assist in identifying patients who would benefit from further counseling about appropriate use of oral oncolytics and management of adverse effects

Trends in Oncology Novel Drug Approvals

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Oncology Novel Drugs Oral Agents

Novel drug approvals for 2020. FDA. Updated January 13, 2021. Accessed February 16, 2021. www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2020

Benefits of Oral Cancer Treatment

Eek D, et al. Patient Prefer Adherence. 2016;10:1609-1621; Mahay H. Oral chemotherapy: patient advantages and challenges. Pharmacy Times. Published August 15, 2009. Accessed February 13, 2021. pharmacytimes.com/publications/issue/2009/August2009/CounselingChemotherapy-0809

Patient convenience

Less invasive

Drug exposure

Ease of dose modification

Decreased health care utilization

Quality of life

Oral Oncolytics for Solid Tumors

Solid Tumor FDA Approvals

Agent Approval Date Target/Mechanism Malignancy

Avapritinib January 9, 2020 PDGFRA and KIT inhibitor GIST

Tazemetostat January 23, 2020 EZH2 inhibitor Epithelioid sarcoma and follicular lymphoma

Selumetinib April 10, 2020 MEK inhibitor Neurofibromatosis type 1

Tucatinib April 17, 2020 HER2 inhibitor Breast cancer

Pemigatinib April 20, 2020 FGFR2 inhibitor Cholangiocarcinoma

Capmatinib May 6, 2020 MET inhibitor NSCLC

Selpercatinib May 8, 2020 RET inhibitor NSCLC and thyroid cancer

Ripretinib May 15, 2020 PDGFRA and KIT inhibitor GIST

Pralsetinib September 4, 2020 (NSCLC), December 1, 2020 (thyroid)

RET inhibitor NSCLC and thyroid cancer

Relugolix December 18, 2020 Oral GnRH antagonist Prostate cancer

Tepotinib February 3, 2021 MET inhibitor NSCLC

Tivozanib March 10, 2021 VEGFR, c-KIT and PDGFRB inhibitor Renal cell carcinoma

FDA. Hematology/Oncology (Cancer) Approvals & Safety Notifications. Updated February 9, 2021. Accessed March 29, 2021. www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications.

GIST, gastrointestinal stromal tumorNSCLC, non-small cell lung cancer

Capmatinib for NSCLC

Metastatic Non−Small Cell Lung Cancer

• 3%-4% of patients have MET exon skipping mutations, 1%-6% have MET amplifications• Oncogenic driver alterations: MET exon 14 skipping mutations, MET gene copy number (GCN) gain or

amplification, MET protein overexpression

• Mutually exclusive with other driver mutations

• MET exon 14 skipping mutations and MET amplifications may occur concomitantly

• High MET amplifications and exon 14 skipping mutations associated with poor prognosis

• Treatment• Crizotinib

• Capmatinib (preferred)

• Tepotinib (preferred)

Wolf J, et al. N Engl J Med. 2020;383:944-957; Vansteenkiste JF, et al. Expert Review of Anticancer Therapy. 2019;659-671; NCCN Guidelines. Non-Small Cell Lung Cancer. V3.2021. Updated March 3, 2021. Accessed March 15, 2021. www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

Capmatinib: GEOMETRY Study• GEOMETRY mono-1 study (NCT02414139)

• Multiple cohort, phase 2 study of capmatinib in patients with MET-dysregulated advanced NSCLC

• 364 patients; 97 patients had MET exon 14 skipping mutation, 210 had MET amplification

• MET Exon 14 Skipping Mutation• Primary end point: OR

• Previously treated (n=69): 41% (95% CI, 29-53)• Treatment naïve (n=28): 68% (95% CI, 48-84)

• Secondary end point: DOR• Previously treated (n=69): 9.7 months (95% CI, 5.6-

13.0)• Treatment naïve (n=28): 12.6 months (95% CI, 5.6-

NE)

• MET Amplification and GCN ≥10• Primary end point: OR

• Previously treated (n=69): 29% (95% CI, 19-41)• Treatment naïve (n=15): 40% (95% CI, 16-68)

• Secondary end point: DOR• Previously treated (n=69): 8.3 months (95% CI, 4.2-

15.4)• Treatment naïve (n=15): 7.5 months (95% CI, 2.6-

14.3)

• Most common AEs (all cohorts): • Peripheral edema (51%), nausea (45%),

vomiting (28%), blood creatinine increased (24%), dyspnea (23%), fatigue (22%), decreased appetite (21%)

• 51% of patients experienced serious AE• 15% led to discontinuation

Wolf J, et al. N Engl J Med. 2020;383:944-957.

Capmatinib showed treatment benefit in patients with advanced NSCLC and a MET exon 14 skipping mutation, particularly in treatment naïve patients

Medication Considerations

Tabrecta. Prescribing information. Novartis Pharmaceuticals Corporation. May 2020.

Indication Adult patients with metastatic NSCLC whose tumors have a MET exon 14 skipping mutation

Dose 400 mg PO twice daily with or without food

Missed Dose Do not make up missed dose; if vomited, skip dose

Formulation 150-mg and 200-mg tablets; dispense in original packaging

Emetic Risk Moderate to high

Dose Modifications Hepatotoxicity, other grade 3/4 adverse reactions (grade 2 if intolerable)Severe hepatic impairment, strong CYP2C8 inhibitors

Drug Interactions Avoid coadministration with strong and moderate CYP3A inducers

Warnings and Precautions

Interstitial lung disease, hepatotoxicity, risk of photosensitivity

Tepotinib for NSCLC

Tepotinib: VISION Study (Cohort A)• Phase 2 open-label study of tepotinib in patients with advanced or metastatic NSCLC with

confirmed MET exon 14 skipping mutation

• 152 patients treated, 99 followed at least 9 months

Paik PK, et al. N Engl J Med. 2020;383:931-943.

Primary end point Combined biopsy (n=99)

Liquid biopsy (n=66)

Tissue biopsy (n=60)

OR after 9 months by independentreview

46% (95% CI, 36-57); no CR, only PR

48% (95% CI, 36-61)

50% (95% CI, 37-63)

Secondary end points

Investigator OR 56% (95% CI, 45-66); 2 CR, 53 PR

56% (95% CI, 43-68)

62% (95% CI, 48-74)

DOR (months) 11 (95% 7.2-NE) 9.9 (95% CI, 7.2-NE)

15.7 (95% CI, 9.7-NE)

PFS (months) 8.5 (95% CI, 6.7-11.0)

8.5 (95% CI, 5.1-11.0)

11.0 (95% CI, 5.7-17.1)

OS (months) 17.1 (95% CI, 12.0-26.8)

________ ________

Patients with brain mets (n=11)

OR 55% (95% CI, 23-83)

DOR 9.5 months (95% CI, 6.6-NE)

PFS 10.9 months (9% 8.0-NE)

• Safety (n=152): 89% any grade AE; peripheral edema (63%), nausea (26%), diarrhea (22%)• 28% grade ≥3 treatment-related AEs;

7% peripheral edema

Tepotinib was associated with treatment response in patients with advanced NSCLC and a confirmed MET exon 14 mutation


Tepmetko. Prescribing information. EMD Serono Inc. February 2021.

Indication Adult patients with metastatic NSCLC whose tumors have a MET exon 14 skipping mutation

Dose 450 mg PO once daily with food

Formulations 225-mg tablet; store in original package (blister cards)

Missed Dose Do not make up if within 8 hours of next dose; if vomited, skip dose

Emetic Risk Minimal to low

Dose Modifications Hepatotoxicity, other grade 3/4 adverse reactions (grade 2 if intolerable)

Drug Interactions Avoid coadministration with dual strong CYP3A inhibitors and P-gp inhibitors, strong CYP3A inducers, and sensitive P-gp substrates with a narrow therapeutic index

Adverse Effects Edema (70%), fatigue (27%), nausea (27%), diarrhea (26%), musculoskeletal pain (24%), dyspnea (20%)


Interstitial lung disease, hepatotoxicity

Capmatinib vs Tepotinib for NSCLC

Tabrecta. Prescribing Information. Novartis Pharmaceuticals Corporation. May 2020; Tepmetko. Prescribing information. EMD Serono Inc. February 2021.

Capmatinib Tepotinib

Drug Targets MET, including mutant variant produced by exon 14 skipping

MET, including variants with exon 14 skipping alterations, melatonin 2 and imidazoline 1

Indication Adult patients with metastatic non−small cell lung cancer whose tumors have a MET exon 14 skipping mutation

Adult patients with metastatic non−small cell lung cancer whose tumors have a MET exon 14 skipping mutation

Dosing 400 mg PO twice daily with or without food 450 mg PO once daily with food

Adverse Effects

Peripheral edema (52%), nausea (44%), fatigue (32%), vomiting (28%), dyspnea (24%), decreased appetite (21%)

Edema (70%), fatigue (27%), nausea (27%), diarrhea (26%), musculoskeletal pain (24%), dyspnea (20%)


Interstitial lung disease, hepatotoxicity, risk of photosensitivity

Interstitial lung disease, hepatotoxicity

Patient Case

JT is a 48-year-old woman with newly diagnosed RET-fusion positive NSCLC. She has a PMH of chronic urinary tract infections and is on ciprofloxacin prophylaxis; she also has depression and is on citalopram. Her baseline QTc is 480 ms. The oncologist has prescribed selpercatinib and JT has an education session scheduled with the pharmacist.

Selpercatinib for NSCLC

RET Activation in NSCLC: RET Fusions

Gautschi O, et al. J Clin Oncol. 2017;13:1403-1410; Lipson D, et al. Nat Med. 2012;18:382-384; Ferrara R, et al. J ThoracOncol. 2018;13:27-45. Kato S, et al. Clin Cancer Res. 2017;23(8):1988-1997; Wang R, et al. J Clin Oncol. 2012;30:4352-4359; NCCN Guidelines. Non-Small Cell Lung Cancer. V2.2021. Updated March 3, 2021. www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

• 1% to 2% of NSCLC

• More common in adenocarcinoma

• Most frequent kinesin family member 5B (KIF5B)–RET chimeric protein juxtaposes KIF5B exon 15 and RET exon 12

• Other common fusion partners: CCDC6, NCOA4, and TRIM33

• Many other fusion partners have also been identified

• Typically, do not occur concurrently with alterations in EGFR, ALK, ROS1, BRAF, or KRAS

• First-line/subsequent therapy: selpercatinib, pralsetinib, cabozantinib, vandetanib

Most Common RET Translocation in Lung Adenocarcinoma: KIF5B-RET

P

P

713575KIF5B

KIF5B exon 15 RET exon 12

Selpercatinib: LIBRETTO-001 Study (NSCLC)

• Phase 1/2 open-label study of selpercatinib in patients with advanced solid tumors, including RET-fusion+ solid tumors, medullary thyroid cancer, and other tumors with RET activation• Safety: grade ≥3 AEs: hypertension (14%), increased

ALT (12%), increased AST (10%), hyponatremia (6%), lymphopenia (6%)• 2% discontinued due to drug-related AEs

Drilon A, et al. N Engl J Med. 2020;383:813-824.

Previous Platinum Chemotherapy (n=105) Previously Untreated (n=39)

Independent Review Investigator Assessment Independent Review Investigator Assessment

OR (95% CI) 64% (12.0-NE) 70% (60-78) 85% (70-94) 90% (76-97)

Median DOR (months) 17.5 (12.0-NE) 20.3 (15.6-24.0) NE (12.0-NE) NE (12.0-NE)

Median PFS (95% CI) 16.5 (13.7-NE) 18.4 (16.4-24.8) NE (13.8-NE) NE (13.8-NE)

1-year PFS (95% CI) 66% (55-74) 68% (58-76) 75% (56-87) 75% (55-87)

Selpercatinib showed durable efficacy and low-grade toxicity in patients with RET-fusion positive NSCLC (including CNS disease) who had been treated with platinum-based chemotherapy or had not received treatment


Retevmo. Prescribing information. Eli Lilly and Company. January 2021.

Indication Adult patients with metastatic RET fusion + NSCLCAdult and pediatric patients ≥12 years with advanced metastatic RET-mutant MTC requiring systemic therapy or RET fusion+ thyroid cancer who require systemic therapy and are radioactive iodine refractory

Dose 120 mg (<50 kg) or 160 mg (≥50 kg) PO twice daily with or without food

Formulations 40-mg and 80-mg capsules



Dose Modifications Hepatotoxicity, hypertension, QT prolongation, hemorrhagic events, hypersensitivity reactions, other grade 3/4 adverse reactions

Drug Interactions Avoid coadministration with strong and moderate CYP3A inhibitors and CYP3A inducers, CYP2C8 and CYP3A substrates, acid-reducing agents


Hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing

Pralsetinib for NSCLC

Pralsetinib: ARROW Study (NSCLC)

• Phase 1/2 study of pralsetinib in patients with thyroid cancer, NSCLC, and other advanced solid tumors

Gainor JF, et al. J Clin Oncol. 2020;38, no. 15_suppl: 9515.

• Safety (n=354): treatment-related adverse effects (TRAEs) primarily grade 1-2• Increased AST (31%), anemia (22%),

increased ALT (21%), constipation (21%), hypertension (20%)

• 4% discontinued due to TRAEs

Overall (n=116) Prior platinum (n=80)

No prior systemic treatment (n=26)

ORR (95% CI) 65% (55-73) 61% (50-72) 73% (52-88)

DCR (95% CI) 93% (CI, 87-97) 95% (88-99) 88% (70-98)

CR 6% 5% 12%

Median Timeto Response

1.8 months ------------------ -------------------

DOR NR (11.3-NR) ------------------- -------------------

Pralsetinib has rapid, potent, and durable clinical activity in patients with advanced RET fusion+ NSCLC, regardless of fusion genotype or

prior treatment


Gavreto. Prescribing information. Blueprint Medicines Corporation. December 2020.

Indication Adult patients with metastatic RET fusion + NSCLCAdult and pediatric patients ≥12 years with advanced metastatic RET-mutant MTC requiring systemic therapy or RET fusion+ thyroid cancer who require systemic therapy and are radioactive iodine refractory

Dose 400 mg PO once daily on an empty stomach (1 hour before or 2 hours after food)

Formulation 100-mg capsules


Missed Dose Take as soon as remembered on the same day; then resume regular schedule

Dose Modifications Interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, other grade 3/4 adverse reactions

Drug Interactions Avoid coadministration with strong CYP3A inhibitors, combined P-gp and strong CYP3A inhibitors, and strong CYP3A inducers

Warnings and Precautions Interstitial lung disease, hypertension, hepatotoxicity, hemorrhagic events, tumor lysis syndrome, risk of impaired wound healing

Selpercatinib vs Pralsetinib

Retevmo. Prescribing information. Eli Lilly and Company. January 2021; Gavreto. Prescribing information. Blueprint Medicines Corporation. December 2020.

Selpercatinib Pralsetinib

Drug Targets wild-type RET and multiple mutated RET isoforms (RET V804M, RET M918T), VEGFR1, VEGFR3, FGFR1, 2, and 3, and RET fusion proteins (CCDC6-RET, KIF5B-RET)

wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M, and RET M918T) in addition to DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB, FGFR1

Indication Adult patients with metastatic RET fusion + NSCLC; adult and pediatric patients ≥12 years with advanced metastatic RET-mutant MTC requiring systemic therapy or RET fusion+ thyroid cancer who require systemic therapy and are radioactive iodine refractory

Adult patients with metastatic RET fusion + NSCLC; adult and pediatric patients ≥12 years with advanced metastatic RET-mutant MTC requiring systemic therapy or RET fusion+ thyroid cancer who require systemic therapy and are radioactive iodine refractory

Dosing 120 mg (<50 kg) or 160 mg (≥50 kg) PO twice daily with or without food

400 mg PO once daily on an empty stomach (1 hour before or 2 hours after food)

Adverse Effects (≥20%)

Dry mouth (39%), diarrhea (37%), hypertension (35%), fatigue (35%), edema (33%), rash (27%), constipation (25%), nausea (23%), abdominal pain (23%), headache(23%)

Constipation (35%-41%), fatigue (35%-38%), musculoskeletal pain (32%-42%), hypertension (28%-40%), diarrhea (24%-34%), cough (23%-27%), pyrexia (20%-22%), edema (20%-29%)


Hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing

Interstitial lung disease, hypertension, hepatotoxicity, hemorrhagic events, tumor lysis syndrome, risk of impaired wound healing

Tivozanib for Renal Cell Carcinoma

Tivozanib: TIVO-3 Study

• Open-label randomized controlled phase 3 trial to compare tivozanib to sorafenib as third- or fourth-line therapy in patients with metastatic renal cell carcinoma (RCC)• MOA: inhibits VEGFR 1, 2, and 3, c-KIT and PDGFR β

• TRAEs: 84%• Grade 3/4: hypertension (20%), asthenia (5%)

• Grade 1/2: diarrhea (33%), fatigue (29%), hypertension (27%), decreased appetite (24%), dysphonia (23%), asthenia (21%)

Rini BI, et al. Lancet Oncol. 2020;21(1):95-104.

Tivozanib (n=175) Sorafenib (n=175)

PFS 5.6 (5.29-7.33) 3.9 (3.71-5.55) HR, 0.73 (0.56-0.94; P=0.016)

OS at 2 years 16.4 (13.4-22.2) 19.7 (15.0-24.2) HR, 0.99 (0.76-1.29; P=0.95)

ORR 18% (12-24) 8% (4-13)

DOR (months) NR (12.9-NR) 5.7 (5.6-NR)

Tivozanib showed improved PFS and was better tolerated than sorafenib as third- or fourth-line therapy in patients with metastatic RCC


Fotivda. Prescribing information. AVEO Pharmaceuticals. March 2021.

Indication Adult patients with relapsed or refractory advanced RCC following ≥2 prior therapies

Dose 1.34 mg once daily with or without food on days 1-21 of 28-day cycle

Formulation 0.89-mg and 1.34-mg capsules


Missed Dose Take the next scheduled day; do not take 2 doses in the same day

Dose Modifications Hypertension, cardiac failure, proteinuria, persistent or intolerable grade 2 or 3 adverse reaction, or grade 4 laboratory abnormality, moderate hepatic impairment

Drug Interactions Avoid coadministration with strong CYP3A inhibitors


Hypertension and hypertensive crisis, cardiac failure, cardiac ischemia and arterial thromboembolic events, venous thromboembolic events, hemorrhagic events, proteinuria, thyroid dysfunction, risk of impaired wound healing, reversible posterior leukoencephalopathy syndrome, allergic reaction to tartrazine (FD&C Yellow No. 5)

Oral Oncolytics for Hematologic Malignancies

Hematologic Malignancy FDA Approvals

Agent Approval Date Target/Mechanism Malignancy

Tazemetostat January 23, 2020/June 18, 2020

EZH2 inhibitor Epithelioid sarcoma and Follicular lymphoma

Decitabine/ cedazuridine

July 7, 2020 Hypomethylator Myelodysplastic syndrome (MDS)

Oral azacitidine

September 1, 2020 Hypomethylator Acute myeloid leukemia (AML) maintenance

Umbralisib February 5, 2021 PI3K-delta and casein kinase inhibitor

R/R marginal zone lymphoma and R/R follicular lymphoma

FDA. Hematology/Oncology (Cancer) Approvals & Safety Notifications. March 23, 2021. Accessed March 29, 2021. www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications.

Umbralisib for R/R Follicular and Marginal Zone Lymphomas

Patient Case

TB is a 68-year-old man with R/R follicular lymphoma. He has been treated with 3 prior regimens. The oncologist has prescribed umbralisib and TB has an education session scheduled.

Umbralisib: UNITY-NHL Trial

• Multicenter, open-label, registration-directed phase 2 study

• Previously treated NHL

• MZL (n=69): R/R to ≥1 prior line of treatment (tx), which must have included anti-CD20

• FL (n=117): R/R to ≥2 prior lines of tx, which had to include anti-CD20 and alkylating agent

• Most common grade ≥3 AEs

• Neutropenia (11.5%), diarrhea (10.1%), increased ALT/AST (7.2%)

• Other AEs of interest

• Pneumonitis (all grade, 1.4%), colitis (all grade, 1.4%)

• 28.1% serious AEs; 24.6% grade ≥3

• TRAEs led to discontinuation: 14.9%

• TRAEs led to dose reduction: 9.6%

Zinzani PL, et al. Blood. 2020;136:34-35. Abstr 2934.

Efficacy Outcome

MZL FL

ORR49.3%

(95% CI, 37.0-61.6%)45.3%

(95% CI, 36.1-54.8%)

CR 15.9% 5.1%

DCR 82.6% 86.4%

Median PFS NR (12.1-NE) 20.9 (95% CI 7.4-24.1

Umbralisib achieved meaningful clinical activity in heavily pretreated patients with indolent NHL with a

manageable safety profile


Ukoniq. Prescribing information. TG Therapeutics. February 2021.

Indication Adult patients with:R/R MZL who have received ≥1 prior anti-CD20-based regimenR/R FL who have received ≥3 prior lines of systemic therapy

Dose 800 mg once daily with food

Formulation 200-mg tablets

Emetic Risk Moderate to high


Dose Modifications Neutropenia, thrombocytopenia, infection, liver function test elevations, diarrhea or noninfectious colitis, severe cutaneous reactions, other severe AEs

Drug Interactions n/a


Infections, neutropenia, noninfectious colitis, hepatotoxicity, severe cutaneous reactions, allergic reaction to tartrazine (FD&C Yellow No. 5)

Select Pipeline Agents and Anticipated Approvals

Notable Pipeline Agents: Breast Cancer

Drug Veliparib Oral paclitaxel/encequidar

Mechanism of Action (MOA)

PARP Inhibitor Encequidar inhibits P-glycoprotein, a drug efflux pump that lowers paclitaxel bioavailability

Disease Sites NSCLC, BRCA1/2 mutation + breast cancer and ovarian cancer

Metastatic breast cancer

Select Trials VEILA trial• BRCA-mutation cohort

• Median PFS: 34.7 months vs 22.0 months

• HRD cohort• Median PFS: 31.9 months vs 20.5

months

Phase 3 trial • ORR was 39% for oral paclitaxel with encequidar vs 24.8% with

intravenous paclitaxel• CR rate was similar • Lower neuropathy and greater GI AEs compared to IV paclitaxel

FDA response (March 1, 2021)• Concerns regarding neutropenia rates and efficacy • Recommended a new clinical trial in patients with metastatic

breast cancer, adding that risk-mitigation strategies–such as dose optimization or exclusion of patients considered to be at high risk of toxicities be implemented to improve the safety profile

Athenex Announces Data on Oral Paclitaxel and Encequidar to be Presented at the 2020 San Antonio Breast Cancer Symposium (SABCS); 2020. https://ir.athenex.com/news-releases/news-release-details/athenex-announces-data-oral-paclitaxel-and-encequidar-be. Accessed February 14, 2021; Coleman, et al. N Engl J Med. 381, 2403-2415; Athenex receives FDA complete response letter for oral paclitaxel plus encequidar for the treatment of metastatic breast cancer. News release. Athenex. March 1, 2021. Accessed March 16, 2021. https://ir.athenex.com/news-releases/news-release-details/athenex-receives-fda-complete-response-letter-oral-paclitaxel

Notable Pipeline Agents: Lung Cancer

Slater H. FDA grants breakthrough therapy designation to sotorasib for NSCLC with KRAS G12C mutation. December 8, 2020. Accessed February 15, 2021. www.cancernetwork.com/view/fda-grants-breakthrough-therapy-designation-to-sotorasib-for-nsclc-with-kras-g12c-mutation; Li BT, et al. CodeBreak 100: Registrational Phase 2 trial of sotorasib in KRAS p.G12C mutated non-small cell lung cancer. Abstract PS01.07. Takeda Announces U.S. FDA Breakthrough Therapy Designation for Mobocertinib (TAK-788) for the Treatment of NSCLC Patients with EGFR Exon 20 Insertion Mutations; 2020. Accessed February 14, 2021. www.takeda.com/newsroom/newsreleases/2020/takeda-announces-u.s.-fda-breakthrough-therapy-designation-for-mobocertinib-tak-788-for-the-treatment-of-nsclc-patients-with-egfr-exon-20-insertion-mutations/

Drug Sotorasib Mobocertinib

MOA KRAS G12C inhibitor EGFR/HER2 exon 20 insertion mutation inhibitor

Disease Sites Locally advanced or metastatic NSCLC with KRAS G12C mutation after ≥1 prior tx

Metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression after platinum-basedchemotherapy

Select Trials Phase 2 CodeBreak 100 study• 126 patients with advanced NSCLC whose cancer

had progressed despite prior chemotherapy and/or immunotherapy

• End points• ORR: 37.4% (95% CI, 28.8-46.6)• DCR: 80.5% (95% CI, 72.4-87.1)• Median PFS: 6.7 months (95% CI, 4.9-8.1)

Phase 1/2 trial • Median PFS: 7.3 months • Confirmed ORR: 43%

PDUFA Date August 16, 2021

Notable Pipeline Agents

Virgil H. fruquintinib enters phase 3 trial for metastatic colorectal cancer. OncLive. December 7, 2020.. Accessed February 15, 2021. www.onclive.com/view/fruquintinib-enters-phase-3-trial-for-metastatic-colorectal-cancer; Bourhis J, et al; GORTEC Investigators. 2020 European Society for Clinical Oncology Virtual Congress; September 19-21, 2020; virtual. LBA39; FDA grants breakthrough therapy designation for Debiopharm’snovel chemo-radio sensitizer 2. Debio 1143 for front-line treatment of head & neck cancer. News release. Debiopharm International SA. February 27, 2020. Accessed February 25, 2021. https://bit.ly/2Vurl1x

Drug Fruquintinib Xevinapant

MOA VEGF inhibitor Inhibitor of apoptosis proteins (IAP)

Disease Sites metastatic colorectal cancer who have received prior fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, VEGF-directed therapy, and if applicable EGFR-directed therapy

Locally advanced squamous cell carcinoma of the head and neck

Select Trials Phase 3 FRESCO trial• 416 patients with previously treated metastatic

CRC were randomized to fruquintinib (n=278) or placebo (n=138)

• End points• OS: 9.3 months vs 6.6 months; HR, 0.65;

95% CI, 0.51-0.83; P <0.001• Median PFS: 3.7 months vs 1.8 months; HR,

0.26; 95% CI, 0.21-0.34; P <0.001

Phase 2 trial of cisplatin-based concomitant fractionation chemoradiation with or without xevinapant• OS: xevinapant 66% (95% CI, 49%-78%) vs placebo 51% (95%

CI, 34%-65%)• PFS at 36 months: xevinapant 72% vs placebo 36%

Oral Oncolytic Patient Education and Management Considerations

Oral Oncolytic Logistics

Timmers L, et al. BMC Cancer. 2017;17(1):122; Mulkerin DL, et al. J Oncol Pract. 2016;12(10):e912-e923; Battis B, et al. J Oncol Pharm Pract. 2017;23(8):582-590; Mackler E, et al. J Oncol Pract. 2019;15(4):e346-e355. Dillmon MS, et al. J Clin Oncol. 2020;38(6):633-644.

Initiation

• Drug-drug interactions

• Inappropriate dosing

• Baseline labs and monitoring

• Need for education

• Insurance and procurement

Coordination

• Cyclic labs

• Methods of communication

• Refills

• Provider appointments

• Updated insurance plans

Maintenance

• AE management

• Adherence and compliance

• Cyclic labs

• Refills

The health care team provides clinical considerations and

operational best practices to optimize oral oncolytic dispensing

and management.

Upon FDA Approval• Staff education

• Place in therapy• Financial programs

• P&T/formulary• REMS program

• EMR/pathways• Patient resources

EMR, electronic medical record; REMS, Risk Evaluation and Mitigation Strategy.

Conclusion

• It is challenging to keep up with new drug approvals in oncology• 19 novel drugs approved in 2020; 12 orally available

• 5 novel drugs approved in 2021; 3 orally available (as of April 23, 2021)

• Agents are being approved with novel mechanisms of action filling unmet needs• Targeted for specific mutations

• As new agents are being approved, it is important to determine optimal place in treatment• First-line vs treatment failure

• There are important disease- and patient-specific factors to consider when implementing a treatment plan and educating patients• Indication, drug-drug interactions, dose modifications, monitoring for adverse effects

FDA. Novel Drug Approvals for 2021. Updated April 23, 2021. Accessed April 23, 2021. www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021

Additional Tools and Resources

• How to keep up with what’s new• FDA update emails

• Organization email updates: ASCO, HOPA, etc

• ClinicalTrials.gov

• Process• Dillmon MS, et al. J Clin Oncol. 2020;38(6):633-644.

• Mackler E, et al. J Oncol Pract. 2019;15(4):e346-e355.

• Patient education and toxicity management• Oral Chemo Ed Sheets: www.oralchemoedsheets.com/

• Chemocare: http://chemocare.com/

https://www.oralchemoedsheets.com/

http://chemocare.com/

pharmacist considerations for new and emerging oral

Documents