DOSING AND ADMINISTRATION GUIDE This brochure will help you become familiar with the dosing and administration of PERJETA® () in the following HER2+ treatment settings: › Early (neoadjuvant and adjuvant) ›

HER2=human epidermal receptor 2. Indications › PERJETA is indicated for use in combination with Herceptin® () and for — the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer (EBC) — the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) at high risk of recurrence › PERJETA is indicated for use in combination with Herceptin and for the treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease IMPORTANT SAFETY INFORMATION BOXED WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity › PERJETA can result in subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive (CHF). Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function › Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception — Verify the status of females of reproductive potential prior to the initiation of PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab — There is a pregnancy pharmacovigilance program for PERJETA. If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, healthcare providers and patients should immediately report PERJETA exposure to at 1-888-835-2555 Additional Important Safety Information PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients Please see additional select Important Safety Information on pages 8 through 10, and the accompanying full Prescribing Information, including BOXED WARNINGS. Neoadjuvant & Adjuvant Dosing Early Breast Cancer (EBC) Dosing

NEOADJUVANT DOSING1 ADJUVANT DOSING1 Patients eligible to begin PERJETA® (pertuzumab) and Herceptin® (trastuzumab) Patients eligible to begin PERJETA and Herceptin and chemotherapy in the and chemotherapy in the neoadjuvant setting: HER2+ locally advanced, adjuvant setting: HER2+ EBC at high risk of recurrence inflammatory, or EBC (node-positive, and/or tumor size >2 cm)

START 1 YEAR UP TO 18 CYCLES*

START FOR 36 CYCLES CONTINUE FOR 1215 CYCLES of PERJETA + Herceptin TO COMPLETE 1 YEAR UP TO 18 CYCLES* PERJETA Herceptin PERJETA PERJETA SURGERY chemotherapy Herceptin Herceptin SURGERY chemotherapy *Or until disease recurrence or unmanageable toxicity, whichever occurs first.

*Or until disease recurrence or unmanageable toxicity, whichever occurs first. Patients should receive a total of 1 year (up to 18 cycles) of PERJETA and Herceptin-based therapy, every 3 weeks, starting on Day 1 of the Patients who begin PERJETA and Herceptin in the neoadjuvant setting first taxane-containing cycle1 should continue to receive PERJETA and Herceptin, every 3 weeks, to complete 1 year (up to 18 cycles) or until disease recurrence or Adjuvant chemotherapy regimens as in APHINITY1: unmanageable toxicity, whichever occurs first.1 Non–-based Neoadjuvant chemotherapy regimens1: 6 cycles of docetaxel** + carboplatin††

NEOADJUVANT SETTING ADJUVANT SETTING Anthracycline-based regimens ‡‡ §§ As in NeoSphere: ‡ 3 or 4 cycles of FEC or FAC, followed by 3 or 4 cycles of docetaxel** or 3 postoperative cycles of FEC and continue IIII 4 cycles of PERJETA + PERJETA + Herceptin to complete 1 year (up to 18 cycles) 12 cycles of weekly paclitaxel Herceptin + docetaxel† of treatment per full Prescribing Information 4 cycles of AC¶¶ or EC,*** followed by 3 or 4 cycles of docetaxel** or 12 cycles of weekly paclitaxelIIII As in TRYPHAENA and BERENICE, respectively: 3 or 4 cycles of FEC,‡ followed by 3 or 4 cycles of ** Docetaxel dosing: 75 mg/m2, which could be escalated to 100 mg/m2 if initial dose was well-tolerated (not escalated 2 PERJETA + Herceptin + docetaxel† in non–anthracycline-based regimens); docetaxel dosing following AC or EC administration: 100 mg/m for 3 cycles or 75 mg/m2 for first cycle and 100 mg/m2 for subsequent 3 cycles, or 75 mg/m2 for 4 cycles. ††Carboplatin dosing: AUC 6. As in TRYPHAENA: ‡‡ 2 2 2

SURGERY Continue PERJETA + Herceptin to FEC dosing: 5-fluorouracil (500-600 mg/m ), epirubicin (90-120 mg/m ), and cyclophosphamide (500-600 mg/m ). 6 cycles of PERJETA + Herceptin + complete 1 year (up to 18 cycles) of treatment §§ FAC dosing: 5-fluorouracil (500-600 mg/m 2), (50 mg/m2), and cyclophosphamide (500-600 mg/m2). docetaxel† + carboplatin§ per full Prescribing Information IIII Paclitaxel dosing: 80 mg/m2. ¶¶ AC dosing: doxorubicin (60 mg/m2) and cyclophosphamide (500-600 mg/m2) every 3 weeks or 2 weeks with GCSF support. *** EC dosing: epirubicin (90-120 mg/m2) and cyclophosphamide (500-600 mg/m2) every 3 weeks or 2 weeks with GCSF support. As in BERENICE: 4 cycles of ddAC,II followed by 4 cycles of PERJETA + Herceptin + paclitaxel¶ Managing , as seen in the APHINITY trial2

† Docetaxel dosing: 75 mg/m2, which could be escalated to 100 mg/m2 if initial dose was well-tolerated (escalation of › Early intervention with loperamide, fluids, and electrolyte replacement were considered docetaxel above 75 mg/m2 is not recommended when administered with carboplatin as in TRYPHAENA). for patients experiencing diarrhea ‡FEC dosing in NeoSphere: 5-fluorouracil (600 mg/m2), epirubicin (90 mg/m2), and cyclophosphamide (600 mg/m2); FEC dosing in TRYPHAENA and BERENICE: 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide › The taxane dose was recommended to be reduced by 1 dose (600 mg/m2). §Carboplatin dosing: AUC 6. level if Grade 3 diarrhea had occurred or unresolved Grade 2 ||ddAC dosing: doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 2 weeks for 4 cycles with GCSF support. diarrhea had required delay of the next chemotherapy cycle ¶Paclitaxel dosing: 80 mg/m2. AUC=area under the curve; ddAC=dose-dense doxorubicin and cyclophosphamide; GCSF=granulocyte colony- stimulating factor.

Please see additional select Important Safety Information on pages 8 through 10, 2 and the accompanying full Prescribing Information, including BOXED WARNINGS. Metastatic Breast Cancer (MBC) Dosing Patient Selection, PERJETA Preparation, Storage and Handling MBC DOSING FROM CLEOPATRA TRIAL1,3 Patient selection1 Patients eligible to begin PERJETA® (pertuzumab) and Herceptin® (trastuzumab) and docetaxel: HER2+ MBC, no previous anti-HER2 therapy or chemotherapy for MBC Assessment of HER2 protein overexpression and gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency. START MINIMUM OF 6 CYCLES

Docetaxel PERJETA is a fixed dose. The same fixed dose should be used for PERJETA + Herceptin 420-mg all patients regardless of body weight. VIAL CONTINUE until disease progression or unacceptable toxicity

Prepare the infusion1 Information Important MBC Dosing & Other › In CLEOPATRA, it was recommended that docetaxel be administered for a minimum of 6 cycles1,3 Administer as an intravenous infusion only. Do not administer as an intravenous push — The recommended initial dose of docetaxel is 75 mg/m2 or bolus. Do not mix PERJETA with other drugs.1 — The docetaxel dose could be decreased by 25% due to toxicity or increased Prepare the solution for infusion, using aseptic technique. Parenteral drug products should to 100 mg/m2 in those patients who could tolerate this dose be inspected visually for particulates and discoloration prior to administration. Withdraw the — Fewer than 6 cycles were allowed for unmanageable toxicity appropriate volume of PERJETA solution from the single-use vial(s). — Comparable docetaxel exposure between the 2 treatment arms in CLEOPATRA3 › Dilute into a 250-mL 0.9% sodium chloride PVC or non-PVC polyolefin infusion bag º Docetaxel was administered for a median of 8 cycles in both treatment arms — Dilute with 0.9% sodium chloride injection only › PERJETA and Herceptin should be continued until disease progression — Do not use dextrose (5%) to dilute PERJETA or unmanageable toxicity1 › Mix diluted solution by gentle inversion. Do not shake › If docetaxel is discontinued, PERJETA and Herceptin may be continued on their own1,3 › Administer immediately once prepared. The diluted sodium chloride infusion solution of PERJETA may be stored at 2°C-8°C (36°F-46°F) for up to 24 hours

Storage and handling1 › PERJETA injection is supplied as a 420-mg/14-mL (30-mg/mL) single-dose vial containing preservative-free solution › Store vials in a refrigerator at 2°C-8°C (36°F-46°F) until time of use › Keep vial in the outer carton to protect from light › NDC 50242-145-01

DO NOT FREEZE. DO NOT SHAKE.

PVC=polyvinyl chloride.

Please see additional select Important Safety Information on pages 8 through 10, 4 and the accompanying full Prescribing Information, including BOXED WARNINGS. PERJETA® (pertuzumab) Dosing Considerations

PERJETA and Herceptin® (trastuzumab) are administered every 3 weeks1 Left ventricular ejection fraction (LVEF)1 Assess LVEF prior to initiation of PERJETA and at regular intervals during treatment to ensure Agent Loading dose Infusion time Subsequent doses Infusion time that LVEF is within normal limits, as indicated. If LVEF declines and has not improved, or has declined further at the subsequent assessment, discontinuation of PERJETA and trastuzumab PERJETA should be strongly considered.

Herceptin 8 mg/kg 90 min 6 mg/kg 30-90 min Dose modifications for left ventricular dysfunction1 Chemotherapy Varies per regimen Varies per regimen Pre- WITHHOLD PERJETA and RESUME PERJETA and treatment Herceptin for at least 3 weeks Herceptin after 3 weeks if › Close observation of the patient is recommended for 30-60 minutes after LVEF: for an LVEF decrease to: LVEF has recovered to: each PERJETA infusion and before any subsequent administration of Herceptin, Either Early breast <50%, with a fall of ≥10% Herceptin HYLECTA™ (trastuzumab and hyaluronidase-oysk), or chemotherapy ≥55%* <10% points below cancer points below pretreatment value ≥50% › If a significant infusion-associated reaction occurs, slow or interrupt the infusion and pretreatment value administer appropriate medical therapies Either Either Metastatic › The infusion should be discontinued immediately if the patient experiences a serious ≥50% 40%-45%, with a fall 40%-45%, with a fall breast cancer <40% of ≥10% points below >45% of <10% points below hypersensitivity reaction pretreatment value pretreatment value

1 * For patients receiving anthracycline-based chemotherapy, an LVEF ≥50% is required after Dose sequencing completion of , before starting PERJETA and Herceptin. › PERJETA, Herceptin, and taxanes should be given sequentially › PERJETA and Herceptin can be given in any order › Taxane should be administered after PERJETA and Herceptin 12 Monitor LVEF prior to initiation and then every ~12 weeks in MBC and EBC › In patients receiving an anthracycline-based regimen, PERJETA and Herceptin should be (once during neoadjuvant therapy). administered following completion of the anthracycline

If a delayed or missed dose of PERJETA with Herceptin occurs1,3,4 › If the time between two sequential infusion cycles is <6 weeks, the 420 mg dose of A subcutaneous, fixed-dose combination with PERJETA + Herceptin PERJETA and the 6 mg/kg dose of Herceptin should be administered. Do not wait until is here.5 Contact your Genentech representative to learn more. the next planned dose › If the time between two sequential infusion cycles is ≥6 weeks, a reloading dose of PERJETA and Herceptin (840 mg and 8 mg/kg, respectively) should be administered

Dose interruption or discontinuation of treatment1 › PERJETA should be discontinued if Herceptin treatment is discontinued Dosing Considerations › Dose reductions are not recommended for PERJETA › For chemotherapy dose modifications, see their respective prescribing information › If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies › The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction

Please see additional select Important Safety Information on pages 8 through 10, 6 and the accompanying full Prescribing Information, including BOXED WARNINGS. Important Safety Information 8 Left Ventricular Dysfunction (LVD) Dysfunction Ventricular Left its excipients PERJETA is contraindicated in patients withInformation Safety known Important hypersensitivity Additional to pertuzumab or to any of BOXED WARNINGS: Left Ventricular andEmbryo-Fetal Dysfunction Toxicity Important Safety Information › › › › › ›

patients treated with PERJETA plus trastuzumab andPERJETA docetaxel plus following trastuzumab FEC; and and FEC, in followed3% of patients by PERJETA docetaxel, plus carboplatin, trastuzumab and and trastuzumab docetaxel; (TCH). in 4% LVD of and occurred docetaxel in 6%following of patients FEC; treated and in 11%with of patientsplus treated trastuzumab with PERJETAand docetaxel; in combination in 16% of withpatients plus treated trastuzumab with PERJETA and 5-fluorouracil, plus trastuzumab epirubicin, andperiod, cyclophosphamide LVEF decline (FEC), >10% followed and a dropby PERJETA to <50% occurredIn the inTRYPHAENA 7% of patients study, treated for patients with PERJETA receiving neoadjuvantin combinationwithtrastuzumabandnopatientstheother3arms treatment, in the overall treatment treated group. Symptomatic LVSD occurred in0.9%ofpatientstreated withneoadjuvantPERJETA with neoadjuvanttrastuzumabanddocetaxel ascompared to 3%ofpatientsinthePERJETA- compared to 8% of patients in the PERJETA-treateddrop group. to <50% LVD occurred occurred in 2% in of 0.9% patients of patients treated treated withIn the neoadjuvant NeoSphere trastuzumabstudy, for and patients docetaxel receiving as neoadjuvantPERJETA-treated group andin2%ofpatientstheplacebo-treated grouptreatment, a LVEF decline >10% and a (LVSD) ventricularsystolic dysfunction left (CHF) occurred in1%ofpatientsthe PERJETA-treated group andin8%ofpatientstheplacebo-treated group. Symptomatic theCLEOPATRAIn study, for patientswithMBC,LVD occurred in4%ofpatientsthe be strongly considered at the subsequent assessment, discontinuation of PERJETA and trastuzumab should that LVEF is within normal limits. If LVEF declines and has not improved, or has declined further Assess LVEF prior to initiation of PERJETA and at regular intervals during treatment to ensure of theserisksandtheneedfor eff contraceptionective Exposure to PERJETA defects. Advise death patients canresult andbirth inembryo-fetal clinically significant ventricular decrease inleft function function prior to and during treatment. Discontinueventricular PERJETA ejectiontreatment fraction for a (LVEF)confirmed and congestivePERJETA heart failurecan result (CHF). in subclinical Evaluate cardiacand clinical cardiac failure manifesting as decreased left trastuzumab andFEC,followed by PERJETA plustrastuzumabanddocetaxel with PERJETA in combination with TCH, and in nonetreated of the with patients PERJETA treated plus trastuzumabwith PERJETA and plusdocetaxel treated following with PERJETA FEC, in 1%in ofcombination patients treatedwith TCH. Symptomatic LVSD occurred in 4% of patients — — and theaccompanying fullPrescribing Information, including Information Safety on pages8through 10, Important Please see additionalselect

to Genentech at1-888-835-2555 healthcare providers PERJETA andpatientsshouldimmediately report exposure 7 monthsfollowing thelastdoseofPERJETA incombinationwithtrastuzumab, pregnancy,during orifapatientbecomespregnant whilereceiving PERJETA orwithin There is a pregnancy pharmacovigilance program for PERJETA. If PERJETA is administered 7 months following the last dose of PERJETA in combinationfemales of reproductivewith trastuzumab potential to use effectiveconception contraception can resultduring intreatment fetal harm, and forincluding embryo-fetalPERJETA deathin combination or birth defects. with trastuzumab Advise during pregnancyPERJETA. Advise pregnant women andfemales ofreproductive potential thatexposure to or within 7 months prior to Verify the pregnancy status of females of reproductive potential prior to the initiation of BOXED WARNINGS.

Hypersensitivity Reactions/Anaphylaxis Infusion-Related Reactions › › › › › › › › ›

(defined as 2 consecutive LVEF measurements aboveheart 50%) failure, at the data47% ofcuto PERJETA-treatedff. The majority patients andpatients 67% of vs placebo-treated 0.2% of placebo-treated patients hadpatients). recovered Of theheart patients failure who with experienced a LVEF declinesymptomatic ≥10% and a dropIn tothe <50% APHINITY was study,<1% (0.6% for of patientsPERJETA-treated treated in the adjuvantdocetaxel following FEC setting, the incidence of symptomatic paclitaxel following ddAC and in none of the patientsFEC. Symptomatictreated with LVSD PERJETA occurred plus intrastuzumab 2% of patients and ddAC treated and inwith 4% PERJETAof the patients plus trastuzumab treated with and PERJETALVD) plus occurred trastuzumab in 7% andof patientsdocetaxel treated following with PERJETAPERJETA plus plus trastuzumab trastuzumab and and paclitaxel docetaxel following following following FEC. Ejection dose-dense fraction doxorubicin decrease and(asymptomatic cyclophosphamide drop (ddAC), to <50% and occurred 2% of patients in 7% of treated patients with treated withIn the PERJETA BERENICE plusstudy, trastuzumab for patients and paclitaxel receiving neoadjuvant PERJETA, LVEF decline ≥10% and a emergency equipment,shouldbeavailable foremergency immediate use has been described in post-marketing reports. Medicationsanaphylaxis to treat and suchfatal reactions, events, have as wellbeen asobserved inPatients patients should treated be withobserved PERJETA. closely Angioedemafor hypersensitivity eventsreactions. were consistent with those observed in CLEOPATRA Severe hypersensitivity, including In the NeoSphere, TRYPHAENA, BERENICE, and APHINITY studies, hypersensitivity/anaphylaxis 3% intheplacebo-treated group v3.0 according to NCI-CTCAE Grades 3-4 hypersensitivity reaction/anaphylaxis was 2% in the PERJETA-treated 11%group in theand PERJETA-treated group and 9% in the placebo-treated group. TheIn incidencethe CLEOPATRA of study, the overall frequency of hypersensitivity reaction/anaphylaxis was reactions infusion severe with patients in discontinuation permanent Consider medical therapies. Monitor patients carefully untilIf acomplete significant resolution infusion of reaction signs and occurs, symptoms. slow or interruptEvents the (NCI-CTCAE infusion v4.0) reactions and wasadminister 1% for the PERJETA appropriate arm and 0.7% for the placeboincidence arm of Grades 3-4 National Cancer Institute–Common Terminology Criteria for21% Adverse of patients in the PERJETA-treated group and in 18% of patients in the placeboday asarm. the otherThe study treatment drugs. For APHINITY, infusion-related reactionsIn the occurredNeoSphere, in TRYPHAENA, and APHINITY studies, PERJETA was administered on the same dysgeusia, hypersensitivity, myalgia, andvomiting the mostcommoninfusionreactionsinPERJETA-treated group (≥1.0%)were fatigue, vomiting. whenalldrugswere thesecondcycle, During administered onthesameday, reactions (≥1.0%)were pyrexia, chills, fatigue, headache, asthenia,hypersensitivity, and placebo-treated group. Less than1%were Grade3or4. The mostcommoninfusion ofinfusionreactions was13%inthePERJETA-treatedfrequency group and10% inthe theCLEOPATRAIn study, onthefirstday, whenonlyPERJETA was administered, theoverall PERJETA hasbeenassociated withinfusionreactions, includingfatalevents 81% of placebo-treated patients recovered at the patientsdata cuto andff in 3% of placebo-treated patients, ofsymptomatic whom 80% of declines PERJETA-treated in LVEF ≥patients10% and aand drop to of<50% the were events reported (86%) werein 3% reportedof PERJETA-treated in anthracycline-treated patients. Asymptomatic or mildly

Important Safety Information (cont’d) Connecting patients to their Genentech medicine › Access Solutions provides helpful access and reimbursement support to assist your patients Most Common Adverse Reactions and practice after a Genentech medicine is prescribed Neoadjuvant Treatment of Breast Cancer › To learn more about Genentech Access Solutions programs and services, call (888) 249-4918 › The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab or visit genentech-access.com and docetaxel administered for 4 cycles were alopecia, neutropenia, diarrhea, and . The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea › The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 3 cycles following 3 cycles of FEC were diarrhea, nausea, alopecia, Talk to eligible patients about enrolling today in Genentech’s Oncology neutropenia, vomiting, and fatigue. The most common NCI-CTCAE v3.0 Grades 3-4 adverse Co-pay Assistance Program reactions (>2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting › Eligible patients with private insurance pay as little as $5 per valid prescription, subject to a › The most common adverse reactions (>30%) with PERJETA in combination with TCH administered maximum benefit of $25,000 for a 12-month period* for 6 cycles were diarrhea, alopecia, neutropenia, nausea, fatigue, vomiting, anemia, and thrombocytopenia. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were The Oncology Co-pay Assistance Program is valid ONLY for patients with commercial insurance who have a valid neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, prescription for a Food and Drug Administration (FDA)-approved indication of a Genentech medication. Patients using Medicare, Medicaid, or any other federal or state government program to pay for their medications are not eligible. fatigue, alanine aminotransferase (ALT) increased, hypokalemia, and hypersensitivity Under the Program, the patient will pay a co-pay. After reaching the maximum Program benefit, the patient will be › The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and responsible for all out-of-pocket costs. paclitaxel administered for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, All participants are responsible for reporting the receipt of all Program benefits as required by any insurer or by law. No fatigue, constipation, peripheral neuropathy, and headache. The most common Grades 3-4 party may seek reimbursement for all or any part of the benefit received through this Program. This Program is void adverse reactions (>2%) were neutropenia, febrile neutropenia, neutrophil count decreased, white where prohibited by law. Genentech reserves the right to rescind, revoke, or amend the Program without notice at any blood cell count decreased, anemia, diarrhea, peripheral neuropathy, ALT increased, and nausea time. Additional eligibility criteria apply. See full terms and conditions at copayassistancenow.com. › The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, Check eligibility and learn more at copayassistancenow.com asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. The most common Grades 3-4 adverse reactions (>2%) were febrile neutropenia, diarrhea, neutropenia, neutrophil count decreased, stomatitis, fatigue, vomiting, mucosal inflammation, neutropenic *For FDA-approved Genentech Oncology therapies. sepsis, and anemia Adjuvant Treatment of Breast Cancer Notes › The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting. ______The most common Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, diarrhea, neutrophil count decreased, anemia, white blood cell count decreased, leukopenia, ______fatigue, nausea, and stomatitis › The incidence of diarrhea, all Grades, was higher when chemotherapy was administered with ______targeted therapy (61% in the PERJETA-treated group vs 34% in the placebo-treated group) and was higher when administered with non–anthracycline-based therapy (85% in the PERJETA-treated ______group vs 62% in the placebo-treated group) than with anthracycline-based therapy (67% in the PERJETA-treated group vs 41% in the placebo-treated group). The incidence of diarrhea during the ______period that was administered without chemotherapy was 18% in the PERJETA-treated group vs 9% in the placebo-treated group References: 1. PERJETA Prescribing Information. Genentech, Inc. 2020. 2. Bines J, Procter M, Restuccia E, at al. Incidence Metastatic Breast Cancer and management of diarrhea with adjuvant pertuzumab and trastuzumab in patients with human epidermal 2-positive breast cancer. Clin Breast Cancer. 2020;20(2):174-181.e3. 3. Baselga J, Cortés J, Kim S-B, et al; › The most common adverse reactions (>30%) seen with PERJETA in combination with trastuzumab CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral 2012;366(2):109-119. 4. von Minckwitz G, Procter M, de Azambuja E, et al. APHINITY Steering Committee and Investigators. neuropathy. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122-131. 5. PHESGO Prescribing Information. Genentech, Inc. 2020. neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see additional select Important Safety Information on pages 8 through 10, 10 and the accompanying full Prescribing Information, including BOXED WARNINGS. © 2020 Genentech USA, Inc. All rights reserved M-US-00007403(v1.0) Printed in USA. 9/20