中部乳癌最終版

(1)

第14回⽇本乳癌学会中部地⽅会教育講演１

固形癌薬物療法の潮流と乳癌の課題

昭和⼤学医学部内科学講座腫瘍内科学部⾨

昭和⼤学腫瘍分⼦⽣物学研究所

飯⽥市⽴病院腫瘍内科

佐々⽊康綱

2017年9⽉9⽇飯⽥市

(2)

Chronological Order of 41 NMEs Approved by

the FDA to Treat Cancer Indications

(2010−2015)

(3)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Chemotherapy Anthracyclines Taxanes Fluorpyrimidines Cyclophosphamide Eribulin Gemcitabin Vinorelbine Fluoropyrimidines Platinum Taxanes Anthracyclines Fluorpyrimidines Oxaliplatin Irinotecan Trifluridine/ tipiracil Platinum Taxanes Fluoropyrimidines Irinotecan Pemetrexed Gemcitabine Vinorelbine Platinum Taxanes Camptothecins Liposomal-Dox Gemcitabine Dacarbazine Hormonetherapy

Enhancer EverolimusPalbociclib

Targeted:

Antibody TrastuzumabPertuzumab Bevacizumab

T-DM1

Trastuzumab

Ramucirumab BevacizumabCetuximab/ Panitumumab Ramucirumab

Bevacizumab

Ramucirumab Bevacizumab

Targeted: TKI Lapatinib Regorafenib Gefitinib/Erlotinib

Afatinib Osimeritinib

Crizotinib/Alectinib

Vemurafenib

Targeted:

PARP-I Olaparib OlaparibRucaparib

Niraparib

Immuno-oncology Nivolumab/Pembrolizumab Nivolumab/Pembrolizumab IpirimumabNivolumab/

(4)

抗悪性腫瘍薬の開発：この10年間の動き

薬剤開発の潮流

n

従来からの化学療法薬の開発が鈍化

n

分⼦標的薬の台頭

• ⼩分⼦製剤

• 抗体薬

n

免疫チエックポイント阻害薬の登場

開発の戦略と実地医療の課題

n

ICHの原則に基づいた世界共同開発

n

第3相試験による全⽣存期間の延⻑

n

バイオマーカーの同定に基づいた対象患

者の絞り込み

n

バイオマーカーを利⽤した薬剤耐性の克

服

n

多彩な有害事象に対する対策

n

費⽤対効果に対する問題意識

(5)

Clinical Endpoints Used in Cancer Trials

(6)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

enhancer EverolimusPalbociclib Targeted:

Antibody TrastuzumabPertuzumab Bevacizumab T-DM1

Trastuzumab

Bevacizumab

Crizotinib/Alectinib Targeted:

Niraparib

(7)

Eribulin vs. TPC in Patients with m-BC

(8)

Eribulin vs. DTIC in Patients with Advanced

Liposarcoma or Leiomyosarcoma

(9)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Enhancer EverolimusPalbociclib Targeted:

Trastuzumab

Bevacizumab

Niraparib

(10)

Potential Combination Strategies for mTOR

and CDK4/6 Inhibitors with Hormone

Therapy.

(11)

BOLERO-2 : Phase III of Everolimus for

Hormone Sensitive BC

(12)

mTOR Inhibitor-Associated Stomatitis (mIAS)

Grade 3への対応

• ⼝腔内の清潔保持の継続

• 医療者による⼝腔ケアの介⼊

• 含嗽の励⾏

• 疼痛緩和の徹底

• 鎮痛薬（アセトアミノフェン、NSAIDs、⻑時

間作⽤型オピオイド、レスキュードーズの併

⽤

• 局所⿇酔薬の使⽤

• 栄養管理

• PEG（胃瘻）や経⿐胃管の使⽤

Grade 4への対応

• 抗がん治療の中⽌

• 有害事象への積極的な治療

• ⼝腔内の清潔保持の継続

• 医療者による⼝腔ケアの介⼊

• 敗⾎症（全⾝感染症）の予防

• 疼痛緩和

• オピオイド持続静注の使⽤

• 栄養管理

• PEG（胃瘻）や経⿐胃管の使⽤

• 中⼼静脈栄養の使⽤

(13)

(14)

Phase III of Palbociclib in HR Positive

Advanced BC: 1

st

_Line

(15)

Phase III of Palbociclib in HR Positive

Advanced BC: 1

st

_Line

(16)

Phase III of Palbociclib in HR Positive

Advanced BC: 2

nd

_Line

n

The primary end point was investigator-assessed progression-free survival.

n

Secondary end points included overall survival, objective response, rate of clinical benefit, patient- reported

outcomes, and safety.

_{N Engl J Med 2015;373:209-19. DOI: 10.1056/NEJMoa1505270}

(17)

Cost-effectiveness of Palbociclib in HR Positive

Advanced Breast Cancer

Ann Oncol 2017; 28: 1825–1831

n

Conclusion: From a societal perspective, PAL treatment of both patient groups (with and without prior

endocrine therapy) is highly unlikely to be cost-effective compared with the usual care in the USA.

(18)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Enhancer EverolimusPalbociclib Targeted:

Trastuzumab

Bevacizumab

Niraparib

(19)

HER2 Overexpressing Cancers

Breast Cancer

Gastric Cancer

(20)

“Basket Trial”

Histology-Independent, Aberration-Specific Clinical Trial

Design

(21)

Sleijfer S et al. JCO 2013;31:1834-1841

“Umbrella Trial”

Histology-Based Clinical Trial Design to Evaluate Multiple

Molecular Aberrations

(22)

“Basket Trial”

Vemurafenib in Multiple Non-melanoma Cancers with

BRAFV600 Mutations

(23)

“Basket Trial”

Vemurafenib in Multiple Non-melanoma Cancers with

BRAFV600 Mutations

(24)

T-DM1 for Trastuzumab Resistant HER2

Overexpressing Cancers

Breast Cancer

Gastric Cancer

(25)

Continuing Trastuzumab Beyond Progression

in HER2 Positive BC

Trastzumab

Taxane

PD

Trastzumab

Capecitabine

PD

Trastzumab

Vinorelbine

Trastzumab

Gemcitabin

PD

(26)

Trastuzumab “Beyond Progression” in HER2–

Positive Advanced BC

(27)

Bevacizumab beyond Progression for CRC

Lancet Oncol 2013; 14: 29–37

BRiTE

(28)

CLEOPATRA

OS and PFS

(29)

Continuing Trastuzumab/Pertuzumab Beyond

Progression in HER2 Positive BC

Trastzumab

Pertuzumab

Docetaxel

PD

Trastzumab

Pertuzumab

Capecitabine

PD

Trastzumab

Pertuzumab

Vinorelbine

PD

Trastzumab

Pertuzumab

Gemcitabin

(30)

Continuing Trastuzumab Beyond Progression

n

During the last decade, most oncologists empirically adopted the practice of continuing

trastuzumab beyond progression of disease in patients with human epidermal growth factor 2

(HER-2) –positive metastatic breast cancer, deviating from the established paradigm of stopping

and switching drugs or interventions when patients develop disease progression.

n

With trastuzumab, they simply switched the cytotoxic agent paired with this monoclonal anti–

HER-2 antibody.

n

This practice was not based on any prospective randomized data establishing

benefit.

Mohammad Jahanzeb JCO 20, 2009 vol. 27 no. 12 1935-1937

(31)

Hormone Receptor-Negative and HER2-Positive Disease

n

Disease progression while receiving trastuzumab

• _{For patients who are receiving treatment with trastuzumab for advanced}

breast cancer,

discontinue treatment with trastuzumab at the time of disease

progression outside the central nervous system.

Do not discontinue

trastuzumab if disease progression is within the central nervous system alone.

NICE Guidance Advanced Breast Cancer: Diagnosis and Treatment

(32)

Trastuzumab “Beyond Progression” in HER2–

Positive Advanced Gastric Cancer

Nobody prescribe Trastuzumab for

gastric cancer in this setting

(33)

Phase II Study of Eribulin Mesylate with

Trastuzumab as First-Line Therapy for HER2-Positive BC

(34)

Patritumab plus Trastuzumab and Paclitaxel

in HER2 Overexpressing m-BC

(35)

Clinical Endpoints Used in Cancer Trials

Endpoints

Regulatory approval

Study design

Overall survival Regular approval (clinical benefit) Randomized studies; masking not essential

Symptom endpoints

(patient-reported outcomes) Regular approval (clinical benefit) Randomized, masked studies

Progression-free survival

(includes all deaths) Accelerated approval or regular approval (surrogate endpoint) Randomized studies; masking preferred in comparative studies; masked review recommended;

Objective response rate Accelerated approval or regular approval

(surrogate endpoint) Single-arm or randomized studies; masking preferred in comparative studies; masked review recommended

(36)

Paclitaxel–Carboplatin ±Bevacizumab for

NSCLC

(37)

Paclitaxel ± Bevacizumab for m-BC

(38)

Avastin No Longer Approved for Breast

Cancer, FDA Says

n

November 18, 2011 — The US Food and Drug Administration (FDA) announced

today that

it is rescinding its approval of bevacizumab (Avastin, Genentech) for

treating metastatic breast cancer because the drug has not proven itself to be

safe and effective for that indication.

(39)

Bevacizumab for Gastric Cancer

AVAGAST Trial

J Clin Oncol 2012; 30: 2119-2127

(40)

(41)

Linear Regression Analysis of Drug Price vs. %

Improvement in PFS and OS

0 20 40 60 80 100 120 140 160 180 0 100 200 300 400 500 600 y=3366x+6.167x106 R2_=1.18x10-2 Improvement of PFS (%) D ru g co st ( x1 0 5 ¥) 0 50 100 150 200 250 300 350 400 0 10 20 30 40 50 60 70 y=-5781x+6.778x106 R2_=1.23x10-4 Improvement of OS (%) Satoh E and Sasaki Y JSMO 2017

(42)

New Model for Assessing Cost-Effectiveness

of Oncology Drugs

Progression-free survival (control)

Progression-free survival (experimental)

Overall survival (control)

Overall survival (experimental)

ΔPFS

ΔOS

Total prices of cancer drugs until disease progression (prescribed drug price: PDP)

Cost Index

_PFS

(¥) = PDP/ΔPFS

Cost Index

_OS

(¥) = PDP/ΔOS

(43)

The Cost Required to Prolong PFS or OS

by 1 Day

0 20 40 60 80 100 120 140 160

PFS

OS

C ost fo r 1 da y pr ol on ga tio n of P F S o r O S ( x1 0 3 ¥)

p = 0.044

Satoh E and Sasaki Y JSMO 2017

(44)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Trastuzumab

Bevacizumab

Niraparib

(45)

Small-Molecule TKIs Approved by the FDA

and the EMA according to Their Indications

(46)

Druggable Somatic Mutation in NSCLC

(47)

EGFR-TKI Sensitive Mutations in NSCLC

(48)

Maemondo M et al. N Engl J Med 2010;362:2380-2388.

NEJ002 Chemo vs. Gefitinib in EGFR

mt

_NSCLC

(49)

EGFR-Tyrosine Kinase Inhibitors

(50)

Lapatinib Plus Capecitabine in Women with

HER-2–Positive Advanced Breast Cancer

ITT Population

Adjusted for ECOG PS

The Oncologist 2010;15:924–934

n

Conclusions. Although premature enrollment termination and subsequent crossover resulted in insufficient power to

detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with

lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2 MBC.

(51)

Acquired Resistance Mechanisms to Combination

Met-TKI/EGFR-TKI Exposure in Met-Amplified

EGFR-TKI–Resistant Lung Adenocarcinoma

(52)

EGFR-TKI Resistant Mutation in NSCLC

(53)

“Liquid Biopsy”

Plasma vs. Tumor Genotyping Assays

Plasma

Cancer tissue

T790M+ (n=158)

T790M- (n=58)

T790M+ (n=129)

111 (70.3 sensitivity)

18 T790M- (n=87)

47

40 (69.0% specificity)

Geoffrey R. Oxnard et al. JCO doi:10.1200/JCO.2016.66.7162

Osimeritinib

(54)

Targeting Agents in Cancer Therapeutics

New Paradigm for Treatment Selection

Target

Tumor

BM

Testing

Drug

Selection

(55)

Phase I of Farletuzumab

PFS and Expression of FRA

(56)

Biomarker Screening in NSCLC

Mutation

Incidence

Effective Drugs

EGFR sensitive mutation

40 % in Asian

Gefitinib/Erlotinib/Afatinib

EGFR resistant mutation

Osimeritinib

EML4-ALK

4-5%

Crizotinib/Alectinib

ROS1

0.5%

Crizotinib

PD-L1

23-28%

Pembrolizumab

(57)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Trastuzumab

Bevacizumab

Niraparib

(58)

Poly (ADP-ribose) Polymerase (PARP) Inhibition as

a Therapeutic Strategy

n

PARP1 and 2 are involved in single-strand breaks.

n

Inhibition of PARP results in “trapping” of protein on DNA, inhibition of replication fork

progression and increased as DNA brakes.

n

Resolution of lesions caused by PARP inhibition dependent on functioning homologous

recombination

n

BRCA1 and BRCA2 are important components of

homologous recombination pathway

n

Cells lacking BRCA1/2 are sensitive to PARP inhibition

(“synthetic lethality” )

in vitro.

(59)

Homologous Recombination:

_{相同組換え}

n

⽣物が⾃ら制御して遺伝情報を再編成することを遺伝的組換え (Genetic

recombination）といいます。遺伝的組換えは，さらに以下の4種類に分けられます。

1. 相同組換え（Homologous recombination）（=普遍的組換え（general recombination））異

なるDNA分⼦間で、相互の分⼦に含まれる同じDNA配列を持つ領域間で⼆本鎖が形成されること

がきっかけとなって分⼦間の再結合が起こることにより、もとのDNA分⼦の鎖が相互に置き換

わった分⼦が形成されること。

2. 部位特異的組換え（Site-specific recombination） [特定の部位で起こる組換え：酵⺟の性転

換や抗体形成過程で⾏われる]

3. トランスポゾン（Transposon）[DNA断⽚が染⾊体上を動き回るような組換え]

4. ⾮正統的組換え（Illegitimate recombination）[上記以外の組換え]

相同組換え（相同的組換え）は，DNAの塩基配列がよく似た部位（相同部位）で起こる組換えです。様々な化学物質や放射線により切断されたDNAは主に相同組換えによって修復されます。また，減数分裂に伴い⾼頻度で起こり、相同組換えがうまくいかないと配偶⼦が形成されません。⽇本⼤学⽣物資源科学部応⽤⽣物科学科核酸・蛋⽩質科学研究室

(60)

Synthetic Lethality :

合成致死性

n

Synthetic lethality（合成致死性）:単独遺伝⼦⽋損では細胞や個体に対する致死性を⽰

さないのに，複数の遺伝⼦の⽋損が共存すると致死性を発揮する現象。

n

創薬標的の場合は、2つの遺伝⼦変異で疾患との相関が強くなる創薬ターゲットを指す。

⼀⽅の遺伝⼦変異をコンパニオン診断薬の標的とし，他⽅の活性を阻害することで治療

薬の開発をめざす創薬の新しいコンセプトとして注⽬されている．

(61)

Strategy for Synthetic Lethality based Cancer

Therapy

(62)

BRCA1/2 Mutations Can Be Present Both in Tumor

and Germline

(63)

Genetic Testing in Ovarian Cancer

The “Dream” Test

GERMLINE

n

BRCA1/2

n

_{All other HRD genes}

n

LYNCH, other syndromic genes (PTEN, STK11,

CDH1, p53) … DICER

TUMOR

n

BRCA1/2

n

_{All other HRD genes}

n

LOH/HRD-type metric/biomarker

n

Meth BRCA1, RAD51C, etc?

n

_{LYNCH genes, MSI, meth MLH1, POLE}

n

MTB (mutation/Mb)

Bradley J. Monk, MD, FACS, FACOG

(64)

Olaparib Maintenance Therapy

in Platinum-Sensitive Relapsed Ovarian Cancer

N Engl J Med 2012;366:1382-92.

n

The patients had recurrent ovarian or fallopiantube cancer or primary peritoneal cancer with high grade

serous features or a serous component, which was platinum-sensitive.

n

BRCA1/2 mutation status was not required.

(65)

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer

1.0

(66)

Maintenance Olaparib in Platinum-Sensitive

Recurrent Ovarian Cancer: Phase II

n

Known BRCA

m

_{status was not required for eligibility, but was established via case report forms documenting}

previous local germline BRCA testing, or via retrospective germline BRCA testing

Lancet Oncol 2016; 17: 1579–89

BRCAm

BRCAwt

(67)

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

N Engl J Med 2016;375:2154-64.DOI: 10.1056/NEJMoa1611310

n

We enrolled two independent cohorts on the

basis of the presence or absence of a

germline BRCA mutation

(gBRCA cohort and

non-gBRCA cohort), as determined on

BRACAnalysis testing (Myriad Genetics).

(68)

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

(69)

FDA-Approved PARP Inhibitors in Ovarian Cancer

n

Olaparib (Dec 19, 2014)

• >3rd line, germline BRCA, treatment

n

Rucaparib (Dec 19, 2016)

• >2nd line, germline and somatic BRCA, treatment

n

Niraparib (March 27, 2017)

• >2nd line, no biomarker, maintenance

(70)

Olaparib for

Metastatic Breast Cancer

in Patients with a Germline BRCA Mutation

n

The patients had HER2-negative metastatic breast cancer that was hormone-receptor positive or

was triple negative.

n

Patients had a confirmed deleterious or suspected deleterious germline BRCA mutation; the

mutation was detected by central testing with BRACAnalysis (Myriad Genetics) in 297 patients

and by local testing in 167 patients.

n

Patients had received no more than two previous chemotherapy regimens for metastatic disease,

N Engl J Med 2017;377:523-33. DOI: 10.1056/NEJMoa1706450

(71)

Olaparib for Metastatic Breast Cancer

in Patients with a Germline BRCA Mutation

(72)

Genetic Testing in Ovarian Cancer

n

NCCN Guidelines Version 1.20171

• [Any] patients with a personal history of invasive [non-mucinous] epitherail cancer [including fallopian, peritoneal]

diagnosed at any age

n

ASCO Expert Statement

• Epithelial ovarian, fallopian, or peritoneal cancer…. Even in

the absence of family history

n

SGO Clinical Practice Statement October 2014

• …. All women with ovarian, fallopian, and peritoneal

carcinoma

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Ovarian Cancer. Version 1.2017. 2. Lu KH et al. J Clin Oncol. 2014;32:833-840. 3. https://www.sgo.org/clinical-practice/guidelines/genetic-testing-for-ovarian-cancer/. Accessed May 24, 2017.

(73)

乳癌に対するPARP阻害薬の対象患者の選択？

BRCA1/2変異を伴う正常細胞

n

Germ line mutation

BRCA1/2変異を伴う癌細胞

(74)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Trastuzumab

Bevacizumab

Niraparib

(75)

がん免疫のメカニズム

n

腫瘍に対する免疫反応はリンパ

節において T 細胞が

腫瘍抗原を認識し活性化され、その

後、活性化されたT細胞が゙

腫瘍部位に到達して腫瘍細胞の排除に働く事で

成⽴する。

n

ヒトには免疫反応の調節メカニズ

ムとして、もともと⾃⼰に対する過剰な免疫反応や正

常組織への障害を抑えるための免疫チェックポ

イント機構が

備わっており、T 細胞が

活

性化すると細胞膜上に発現される CTLA-4 や PD-1 が

、抗原提⽰細胞上の CD28 リガ

ンド

ファミリーと結合する事で

、免疫反応が

鎮静化される。

n

腫瘍環境で

はこの免疫チェックポ

イント機構が

増強しており、腫瘍細胞上の CD28 リガ

ンド

ファミリーと活性化リンパ

球の CTLA-4 や PD-1 が

結合する事で

腫瘍免疫の抑制反

応が

起こり、免疫反応による抗腫瘍効果からの回避が

可能となっている。

東みゆき医学の歩み 2013年3⽉2⽇ p.809-815 京都⼤学医学研究科呼吸器内科/腫瘍薬物治療学講座永井宏樹先⽣の総説を改変

(76)

Immune Checkpoints and Inhibitors

NATURE 497, 7 Nov. 京都⼤学本庶佑教授

(77)

Phase I Study of Nivolumab

(78)

Clinical Response of Nivolumab in Melanoma

Patients : “Spider Plot”

N Engl J Med 2012;366:2443-54.

Disease progression

Pseudo progression

Long term disease

stabilization

Complete response

N Engl J Med 2012;366:2443-54.

(79)

LB Alexandrov et al. Nature 500, 1-7 (2013) doi:10.1038/nature12477

The Prevalence of Somatic Mutations across

Human Cancer Types.

(80)

PD-L1 Expression in NSCLC

KEYNOTE-001

N Engl J Med 2015;372:2018-28. DOI: 10.1056/NEJMoa1501824

Proportion score of less than 1% (Panel A), a score of 1 to 49% (Panel B), and a

score of at least 50% (Panel C)

(81)

PD-L1 Expression in NSCLC as a Predictive

Factor of Pembrolizumab?: KEYNOTE-001

(82)

Pembrolizumab vs. Chemotherapy for PD-L1–

Positive NSCLC

(83)

PD-L1 Expression in TNBC

(84)

Pembrolizumab in Patients with Advanced

TNBC: Phase Ib : KEYNOTE-012 Study

Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, There was evidence of an

increasing probability of response (one-sided P = .028 for ORR) and a reduction in the hazard (one-sided P = .012 for PFS) with increasing expression of PD-L1. _{J Clin Oncol 2016; 34:2460-2467.}

(85)

Tumor Response in Patients with dMMR/

MSI-H m-CRC

(86)

PD-1 Blockade by Nivolumab in Tumors

with Mismatch-Repair Deficiency: CM 142

(87)

FDA Approvals Timeline for Solid Tumor

(88)

MSI-H Frequency by Site

(89)

The Clinical Spectrum of Immune Related

Adverse Events

(90)

中部乳癌最終版

第14回⽇本乳癌学会中部地⽅会 教育講演１

固形癌薬物療法の潮流と乳癌の課題

昭和⼤学医学部内科学講座腫瘍内科学部⾨

昭和⼤学腫瘍分⼦⽣物学研究所

飯⽥市⽴病院腫瘍内科

佐々⽊ 康綱

2017年9⽉9⽇ 飯⽥市

Chronological Order of 41 NMEs Approved by

the FDA to Treat Cancer Indications

(2010−2015)

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

抗悪性腫瘍薬の開発：この10年間の動き

薬剤開発の潮流

n

従来からの化学療法薬の開発が鈍化

n

分⼦標的薬の台頭

•

⼩分⼦製剤

•

抗体薬

n

免疫チエックポイント阻害薬の登場

開発の戦略と実地医療の課題

n

ICHの原則に基づいた世界共同開発

n

第3相試験による全⽣存期間の延⻑

n

バイオマーカーの同定に基づいた対象患

者の絞り込み

n

バイオマーカーを利⽤した薬剤耐性の克

服

n

多彩な有害事象に対する対策

n

費⽤対効果に対する問題意識

Clinical Endpoints Used in Cancer Trials

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Eribulin vs. TPC in Patients with m-BC

Eribulin vs. DTIC in Patients with Advanced

Liposarcoma or Leiomyosarcoma

Development of Oncology Drugs

Category

Breast

Gastric

CRC

NSCLC

Ovary

Melanoma

Potential Combination Strategies for mTOR

and CDK4/6 Inhibitors with Hormone

Therapy.

BOLERO-2 : Phase III of Everolimus for

Hormone Sensitive BC

mTOR Inhibitor-Associated Stomatitis (mIAS)

Grade 3への対応

•

⼝腔内の清潔保持の継続

•

医療者による⼝腔ケアの介⼊

•

含嗽の励⾏

•

第14回⽇本乳癌学会中部地⽅会教育講演１

佐々⽊康綱

2017年9⽉9⽇飯⽥市

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