heinshansen.ppt

Second-line treatment in action

Heine HansenNational University Hospital, Copenhagen, Denmark

Case study 1

Case kindly provided by:

Dr Wolfgang Schütte

Städtisches Krankenhaus Martha-Maria Halle Dölau, Germany

Case study 1

• 78-year-old female, Caucasian, non-smoker; PS 2

• Poorly-differentiated adenocarcinoma– stage T3N2M0 (IIIA)

• Three cycles vinorelbine/carboplatin: no remission

• General physical condition considered too poor for second-line chemotherapy

• Treatment with Tarceva 150mg/day was initiated

Case study 1 (cont’d)

After 2 months of Tarceva (complete remission)

PS 0

Start of treatment

PS 2

Striking tumour response and clinical improvement How long should treatment be maintained?

Follow-up after 10 months• Complete remission

maintained; good PS• Corroborates use of

continued treatment in absence of disease progression

Case study 1 (cont’d)

• If rash occurs, do not automatically stop Tarceva• Important to verify proper dosing and administration

Moderate SevereMild

Grade 3/4

<9% patients in BR.21 (n=731)1

12% patients in TRUST* (n=2,412)2

*Single-arm, multicentre, phase IV study of Tarceva 150mg/day in patients with advanced NSCLC who had failed or were not suitable for chemotherapy

1Shepherd FA, et al. N Engl J Med 2005;353:123–322Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190)

Management of rash

Consider dose reduction/interruption

Consider rash treatment strategies

From start of therapy: twice daily application of alcohol-free emollient cream to entire body, and sunscreen to exposed skin, may help prevent

skin reactions

Moderate SevereMild

Management of rash (cont’d)

Management recommendations for symptomatic rash (assess every 2 weeks)

Hydrocortisone1–2% cream

OR

Clindamycin gel or cream, if infected

Synthetictetracycline*

AND

*Doxycycline 100mg b.i.d.†Prednisone, methylprednisolone 30mg once daily (tapered over 30 days)

Treat as moderate

Systemic steroids†

Consider dose interruption

AND

AND

Hydrocortisone1–2% cream

No treatment

OR

Moderate SevereMild

Case study 1 (cont’d)

• Grade 3 rash occurred

• Dose reduced to 100mg after 3 weeks on therapy

• Dose reduced to 50mg after a further month

• Complete remission of rash after 4 weeks– dose increased to 100mg

• In the TRUST study of Tarceva 150mg/day (n=2,041), dose reductions due to erlotinib-related rash were necessary in only 8% of patients1

1Reck M, et al. J Clin Oncol 2006;24(Suppl. 18):411s (Abs. 7190)

Case study 2

Case kindly provided by:

Prof Jean-Charles SoriaInstitut Gustave Roussy, Villejuif, France

Case study 2

• 61-year-old female, Caucasian, never-smoker; PS 1

• October 2004: lung adenocarcinoma– stage T2N0M1 (IV)

• brain metastases

Case study 2 (cont’d)

• Total brain radiotherapy (10 sessions), followed by five cycles of cisplatin + vinorelbine

• Chemotherapy discontinued due to grade 3 anorexia and deterioration in PS

• Partial response in lung and brain (March 2005)

• June 2006: progression in lung– confusion, secondary to carcinomatous leptomeningitis

Case study 2 (cont’d)

• Patient received high-dose steroids– slight improvement

• Treatment initiated with Tarceva 150mg/day– confusion improved within 72 hours– disappearance of carcinomatous cells in cerebrospinal fluid

Before treatment After 9 weeks of Tarceva

Case study 2 (cont’d)

Case study 2 (cont’d)

Before treatment After 9 weeks of Tarceva

Case study 2 (cont’d)

• December 2006: progressive disease (PD), new medullary lesions

• January 2007: confusion; increase of medullary lesions

• Tarceva 300mg/day no improvement

• Reappearance of carcinomatous cells in cerebrospinal fluid

• Rapid global status degradation

• Treatment stopped; BSC

Small retrospective case series of EGFR TKIs in patients with brain metastases

Responders Survival (months)

n=14 6 9.1

n=57 19 13.4 (responders)

6.1 (non-responders)

Hotta K, et al. Lung Cancer 2004;46:255–61Chiu C-H, et al. Lung Cancer 2005;47:129–

38

Ongoing studies of Tarceva in patients with brain metastases

Study Phase Treatments

RTOG-0320 Pilot Assess level of Tarceva in cerebrospinal fluid

NCT00385398 II Stereotactic radiosurgery, temozolomide, Tarceva

NCT00096265 III WBRTWBRT + stereotactic radiosurgery + temozolomideWBRT + stereotactic radiosurgery + Tarceva

NCT00268684 III WBRT + SRSWBRT + SRS + temozolomideWBRT + SRS + Tarceva

SRS = somatostatin receptor scintigraphy; WBRT = whole brain radiotherapy

Source: www.cancer.gov

Case study 3

Case kindly provided by:

Prof Tudor-Eliade Ciuleanu

Cancer Institute Ion Chiricuta, and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania

Case study 3

• 53-year-old female; 15 cigarettes/day for 23 years; PS 1

• Right lower lobe tumour (CT scan; 7–8cm) with carinal invasion

• Multiple enlarged mediastinal lymph nodes (1–1.5cm)

• Adenocarcinoma (bronchoscopy)– stage T4N2M0 (IIIB)

Case study 3 (cont’d)

• Three cycles of etoposide + cisplatin, followed by RT(30 Gy/10 fractions for 12 days) SD

• PD after 4 months; tumour size 12cm; PS worsened (PS 2)

severity of cough, dyspnoea, pain, haemoptysis

• Chemotherapy discontinued

Case study 3 (cont’d)

• Patient requested a trial with Tarceva (entered into BR.21 study)

• Tarceva 150mg/day initiated

• Cough and pain improved (grade 21); haemoptysis resolved; fatigue remained stable

• Self-rated QoL was stable, as was performance status (PS 2)

• Grade 1 stomatitis (resolved spontaneously after 2 months)

• Mild (grade 1) facial rash throughout treatment; no discomfort

Case study 3 (cont’d)

• Best response was SD; maintained for 6 months during continuous treatment with Tarceva

• After 6 months a CT scan showed PD and Tarceva was discontinued

• 3 months later, the patient agreed to receive three cycles of docetaxel 75mg/m2 every 3 weeks SD

• Subsequently remained stable and survived >3 years after starting Tarceva

Radiographic response to Tarceva is not required to obtain a survival benefit (BR.21)

Tarceva Placebo

nMedian survival* n

Median survival* HR p value

SD/PD 367 7.4 204 6.7 0.82 0.037

*Months

OSI Pharmaceuticals and Roche; data on file

Key learnings

• Tumour response is not essential to benefit from Tarceva

• Tarceva has a favourable tolerability profile versus chemotherapy– rash is easily managed and does not usually affect

patients’ daily lives

• Tarceva produces important symptom and QoL benefits

• Tarceva may have a role in the treatment of patients with central nervous system metastases