1235PD - PARAMOUNT: descriptive subgroup analyses of final overall survival (OS) for the phase III study of maintenance pemetrexed (PEM) versus placebo (PLB)...

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Martin Reck
Authors M. Reck1, L. Paz-Ares2, F. De Marinis3, O. Molinier4, T. Prasad Sahoo5, E. Laack6, W. John7, A. Zimmermann7, C.M. Visseren-Grul8, C. Gridelli9
  • 1Thoracic Oncology, Hospital Grosshansdorf, DE-22927 - Grosshansdorf/DE
  • 22instituto De Biomedicina De Sevilla, University Hospital Virgen del Rocío, Seville/ES
  • 31 Unità Operativa Di Pneumologia Oncologica, Azienda Ospedaliera S. Camillo Forlanini, IT-00151 - Rome/IT
  • 4Oncology, Le Mans Regional Hospital, Le Mans/FR
  • 5Oncology, Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal/IN
  • 6Oncology, Ambulantes Krebszentrum Hamburg, DE-22527 - Hamburg/DE
  • 7Oncology, Eli Lilly and Company, Indianapolis/US
  • 8Medical, Eli Lilly, RA Houten/NL
  • 9Medical Oncology, UO Oncologia Medica"S.G. Moscati Hospital", IT-83100 - Avellino/IT

Abstract

Background

PARAMOUNT demonstrated that pem continuation maintenance significantly reduced the risk of disease progression (HR = 0.62) and death (HR = 0.78) versus plb in patients (pts) with advanced NS NSCLC. Preplanned subgroup analyses by baseline characteristics revealed the OS results were consistent, with benefit seen across all subgroups. Here we present descriptive subgroup analyses of the final OS data.

Methods

939 pts received induction therapy (4 cycles pem 500 mg/m2 and cis 75 mg/m2 on day 1 of 21-day cycles), after which 539 pts who had not progressed and had an ECOG performance status (PS) of 0/1 were randomized (2:1) to maintenance pem (500 mg/m2, on day 1 of 21-day cycles) or plb until disease progression. All pts received vitamin B12, folic acid, and dexamethasone.

Results

Pt characteristics were well balanced between arms. The table summarizes baseline characteristics for pts on the pem arm surviving 6-24 months after randomization. Characteristics of pts surviving for longer periods were comparable to those of pts surviving shorter periods, suggesting OS benefit for all subgroups of pts on maintenance therapy. PS, a known prognostic factor, was the only baseline characteristic associated with improved OS. On the pem arm, the percentage of pts with an induction response of complete/partial (CR/PR) versus stable disease (SD) was consistent over time. An additional analysis showed no correlation between the percent of tumor shrinkage with final OS (rho <0.1), showing that tumor response to induction is not an indicator of OS.

Conclusions

In PARAMOUNT, the OS benefit was seen across all subgroups. Other than PS, no baseline or clinical parameter clearly identifies a subgroup more likely to benefit. Maintenance treatment decisions should be made on an individual basis.

Baseline characteristics for pts surviving at least
Baseline 6 mos 12 mos 18 mos 24 mos
Pemetrexed Arm Pts
Median age, yrs 61 61 62 62 63
Age <65, % pts 66 65 62 62 61
Male, % pts 56 55 54 47 49
Caucasian, % pts 94 95 96 96 96
Smoker, % pts
Ever smoker 76 72 69 66 68
Never smoker 23 27 30 33 30
ECOG PS, % pts
0 32 39 42 46 53
1 68 61 59 54 47
Stage IV, % pts 91 92 92 92 90
Histology, % pts
Adenocarcinoma 86 89 89 88 89
Large cell 7 6 7 7 6
Induction response, % pts
CR/PR 44 44 45 48 47
SD 53 55 54 50 51
PD/Unknown 3 1 2 2 3
Placebo Arm Pts
Induction response, % pts
CR/PR 42 40 42 49 52
SD 53 55 54 47 44
PD/Unknown 6 5 4 4 4
Disclosure

M. Reck: Have served as an adviser or consultant to Eli Lilly and Company.

L. Paz-Ares: Have served as an adviser or consultant to Eli Lilly and Company.

O. Molinier: Have served as an adviser or consultant to Eli Lilly and Company.

W. John: Employed by and own stock in Eli Lilly and Company.

A. Zimmermann: Employed by and own stock in Eli Lilly and Company.

C.M. Visseren-Grul: Employed by and own stock in Eli Lilly and Company.

C. Gridelli: Have served as an adviser or consultant to Eli Lilly and Company.

All other authors have declared no conflicts of interest.