Small Cell Lung Cancer Flashcards
How common is small cell lung cancer amongst all the lung cancers?
15-20%
What is the expected RR to fist line combination chemotherapy?
50-70%
What is the prognosis for small cell lung cancer?
Limited stage:
OS 14-20months
5y OS at best 10%
Extensive stage:
OS 8-13m
5y OS
Is RT important in the treatment of limited-stage SCLC?
Pignon 1992 NEJM
Meta-analysis 13 RCTs, 2500 patients
Excluded extensive disease
Compared Chemo alone vs Combined ChemoRT
CONCLUSIONS:
1) Thoracic RT led to 14% reduction in the mortality rate (p sig) = 5% increase in the 3y survival rate
2) Benefit of RT was greatest in those
CAV vs EP for extensive stage SCLC. Which is better and why?
Bruce Roth JCO 1992
2 Aims:
(1) Determine the efficacy/toxicity of CAV and EP
(2) Whether the rapid alternation of CAV and EP would be superior to either regimen alone.
N=400
3 arms:
(A) EP X 4 (12 weeks)
(B) CAV (18 weeks)
(C) CAV/EP (18 weeks)
RESULTS:
RR ~ 50-60%
Cisplatin vs Carboplatin. Any difference?
Seems to be equivalent in terms of efficacy, but different toxicity profile.
2 studies.
1) Skarlos Annals of Oncology 1994
N=150; 2 arms: EP vs EC
Included both limited and extensive stage disease, with Limited stage Responders and ext stage CR receiving RT from #3 onwards + PCI
CDDP more toxic with leukopenia, neutropenia infections, nausea/vomiting, neurotoxicity, hypernergic reactions
CRR 57% and 58%
Survival 12.5m vs 11.8m
2) Rossi JCO 2012 Meta-analysis 4 RCTs with 650 patients. Med OS 9.6m (CDDP) vs 9.4m Med PFS 5.5 vs 5.3m ORR 67% vs 66% Hematologic toxicity higher with Carbo Non-hematologic toxicity higher with CDDP
How can we intensify the dose? Any benefit?
Slight improvement in efficacy,but increased toxicity and mortality
1) Adding drug –> Triplet. Regimens tried:
- Paclitaxel/Etoposide/Carbo
- Carbo/Etoposide/Vincristine
- Paclitaxel/Etoposdie/CDDP
2) Dose Dense
- 2weekly vs 3-weekly ACE
- 2weekly vs 4weekly ICE
- High vs low dose ICE, supports with PBPCs
3) Transplant
- Ifosfamide/Etoposide/Epiruicin/CDDP + APSCT
What are the triplet therapies that you know about?
(A) Lung Cancer 2006, Reck et al Pac/Carbo/Etoposide > Vincristine/Carbo/Etoposide N=600 Stage I-IV SCLC Med OS 12.5m vs 11.7 5y OS 14% vs 6%
(B) 2001 Annals of Oncology Mavroudis
Paclitaxel/Etoposide/CDDP vs Etoposide/CDDP
N=130, tx-naive SCLC (LD and ED)
Trial terminated early due to toxicities
- 8 toxic deaths in TEP arm, vs 0 in EP arm
CR+PR similar at 50%
Duration of response, 1y OS and OS similar in both arms
Med TTP 11m (TEP) vs 9m (p sig)
What dose dense regimens do you know?
1) Thatcher JCO 2000 N=400 - 2 arms: > Doxorubcin/Cyclophosphamide/Etoposide (ACE) q2w + GCSF > ACE q3w - Results: > CRR 40% (GCSF) vs 30% (P sig) - ORR ~80% - 1y OS 50% (G) vs 40% - 2y OS 13% vs 8%
2) Lorigan et al JNCI 2005
SCLC prognostic score 0-1
N=300
2 arms:
- Ifosfamide/Carboplatin/Etoposide (ICE) q4w
- ICE q2w + GCSF + blood-progenitor-cell support
Results:
- ORR 80% vs 88% (Q2w) p not sig
- Med OS ~ 14m
- 2y OS 20% ~
- No. Of neutropenic sepsis stat sig in standard arm
Any role for maintenance chemo in SCLC?
Yes: 1) Bozcuk Cancer 2005 - Meta-analysis of 14 RCTs, n=2500 - maintenance chemo improved 1y OS by 9% (30% to 39%) and 2yOS from 10 to 14% ========== No 1) Rossi - Lung Cancer 2010 Meta-analysis of 21 RCTs, n= 3700 No statistical advantage in OS or PFS for maintenance/consolidation therapy.
Even with the other targeted agents, at most PFS improved, but no OS benefit
Other agent tried:
1) HOG by Hanna Onco 2002
- Maintenance oral Etoposide X 4m after #4 EIP in ext SCLC
- no OS benefit. PFS benefit
2) ECOG study by Schiller JCO 2001
- Maintenance Topotecan x3m after 4# EP in ext stage
- PFS bentter, no OS benefit
3) Temsirolimus - no benefit
4) Continuation maintenance with Irinotecan after induction IP - no benefit
For limited stage SCLC, which is better? Concurrent or sequential CRT and why.
Concurrent is better
1) Takada JCO 2002 (JCOG 9104) N=200 2arms: - Concurrent CRT where RT starts with #1 chemo - Sequential Chemo--> RT RT: 45 Gy BD over 3 weeks 1.5Gy BD EP x4 Concurrent yielded better survival than RT Med survival 20m vs 27m (concurrent arm) 5y OS 24% vs 18% Oesophagitis 9% in CRT vs 4% in seq
How about the role of hyper fractionation of RT? Any value?
2 studies, 1 with OS benefit, one without.
With OS benefit: 1) Turrisi NEJM 1999 EP X 4. 2 arms: - Concurrent 45 Gy BD RT - concurrent 45 Gy OD RT Results: - Median OS 23m vs 19m (OD) - 5y OS 26% (BD) vs 16% - oesophagitis worse with BD RT 27% vs 11%
Without OS Benefit: Schild Int J Radiat Oncol Bio Phys 2004 All s/p 3#EP, then randomize to 2 arms: - 2EP + Daily RT - 2EP + Split course BD RT Then #6 EP then PCI Results: - OS 21m both arms - 5yOS 20%~ - G3 oesophagitis worse in BD RT; G toxicity in 3% with BD RT
How frequent are asymptomatic brain mets in ES-SCLC?
15%
PCI in ES-SCLC. Any role?
(1) Seto ASCO 2014 published JCO 2014
N=160, study closed early after interim analysis showing futility.
As long with response to 1st line platinum-doublet chemo, randomized to:
- PCI (25Gy 10#)
- observation
Brain MRI prior to enrollment required.
Results:
- med OS 10m for PCI and 15m for Obs
PCI significantly reduced the risk of brain mets as compared to Obs 30% vs 60%
PFS 2m~
Conclusion: PCI after response to chemo had a negative impact on OS in pts with ES-SCLC
(2) Ben Slotman EORTC NEJM 2007
ES-SCLC, n=300
s/p chemo with response, randomized to 2 arms:
- PCI
- Observation control top.
Results:
- s/p PCI - lower risk of symp brain mets HR 0.3, p sig
- cumulative risk of brain mets 1y = 15% (PCI) vs 40%
- med DFS 12w to 15w (PCI)
- med OS 5.4m to 6.7m (PCI)
- 1y OS 27% vs 13% (obs)
What about PCI in LS-SCLC?
Yes, role is present.
1) Auperin NEJM 1999
- meta-analysis of 7 trials
- PCI vs observation after CR from chemo
- 5% increase in 3yOS from 15% to 20%, reduces brain mets incidence
2) Arriagada 2002 Ann Oncol
- PCI vs no PCI in those achieving CR
- both LS and ES
- Reduced rate of brain mets from 60% to 40%
- OS ~15%
3) Patel Cancer 2009
- SEER database, retrospective analysis
- n=670
- LS-SCLC s/p PCI
- those receiving PCI had almost double OS at 5y 10% vs 20%
4) Schild Ann Oncol 2012
- pooled analysis
- PCI in pt achieving SD/better after chemo/ChemoRT for both ES and LS
- 3y OS 18% vs 5% (sig)
5) Gregor EJC 1997
- LS-SCLC with CR to induction randomized to PCI vs observation
- reduced brain met, non-sig OS advantage
