Download in patients with advanced nonsquamous non small cell lung cancer

Lung cancer : Key messages from ASCO 2011
Maintenance therapy :
Paz-Ares Lget al. J Clin Oncol 29: 2011 (suppl; abstr CRA7510)
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10
2&abstractID=78420
Conclusion : Maintenance therapy with pemetrexed (PEM) improves progression-free
survival (PFS) in patients with advanced nonsquamous non small cell lung cancer
(NSCLC) not progressive after PEM-cisplatin induction therapy and is well tolerated
(PARAMOUNT).
Comment : This study confirms the importance of maintenance treatment in some
selected patients with non small cell lung cancer. This might be true for targeted agents
but for chemotherapy too.
The induction phase of the trial, consisted in four cycles of induction PEM (500 mg/m2) and
cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Pts who had not progressed during PEMcisplatin induction, ECOG 0/1 were randomized to PEM (500 mg/m2 on day 1 of a 21-day
cycle) plus BSC (n=359) or placebo plus BSC (n=180) until disease progression. PEM
continuation maintenance resulted in a 36% reduction in the risk of progression (HR=0.64,
95% CI: 0.51-0.81; P=0.00025). The disease control rate (% pts with response/stable disease)
was 71.8% on the pem arm, and 59.6% on the placebo arm (P=0.009). The drug-related
serious adverse event (AE) rate was 8.9% on the pem arm, and 9.2% of pts had grade 3/4
laboratory Common Toxicity Criteria AEs. On the placebo arm, the rates were 2.8% and
0.6%, respectively.
Targeted therapy :
Rosell R. J Clin Oncol 29: 2011 (suppl; abstr 7503)
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10
2&abstractID=78285
Conclusion : Erlotinib as first-line treatment for advanced chemonaive non small cell
lung cancer (NSCLC) patients with EGFR mutations improves progression-free
survival (PFS), with acceptable toxicity, compared to platinum-based chemotherapy
(EURTAC).
EGFR tyrosine kinase activating mutations are present in 10-26% of NSCLC tumors and are
associated with increased response to gefitinib and erlotinib. From February 2007 to January
2011, 1,227 patients wer screened for EGFR mutations, and 174 patients were randomly
assigned to receive erlotinib or platinum-based CT. The primary endpoint was PFS. Interim
analysis was done on 153 patients (76 CT, 77 erlotinib) Response rate was 10.5% to CT vs
54.5% to erlotinib (P<0.0001). PFS in the CT arm was 5.2 months (m) (95%CI, 4.4-5.8 m)
compared to 9.4 m (95%CI, 7.9-12.3) in the erlotinib arm (HR, 0.42; P<0.0001). Median
survival was 18.8 m in the CT arm and 22.9 m in the erlotinib arm (HR, 0.80; P=0.42). Most
common toxicities were asthenia (68.9%), anemia (45.9%), nausea (40.5%) and neutropenia
(36.5%) in the CT arm, and diarrhea (57.3%), asthenia (53.3%), and rash (49.3%) in the
erlotinib arm.
Zhang L. J Clin Oncol 29: 2011 (suppl; abstr LBA7511)
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10
2&abstractID=78381
Conclusion : Gefinitib (G), given as maintenance therapy in Chinese patients with
advanced non small cell lung cancer who have received 4 cycles of standard platinumbased chemotherapy without progression/unacceptable toxicity, improves progressionfree survival (PFS) (INFORM).
Patients were randomized 1:1 to G 250mg/day or P on discontinuation of first-line therapy.
296 pts (n=148 G, n=148 P) were randomized (September 2008-August 2009). Median
duration of follow-up was 16.8 months: 91% pts progressed; 59% deaths. G improved PFS,
the primary endpoint (HR=0.42; 95% CI 0.32-0.54; p<0.0001; median PFS 4.8 vs. 2.6
months).
Implications of recent biological results :
Kris MG. Et al. J Clin Oncol 29: 2011 (suppl; abstr CRA7506)
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10
2&abstractID=81670
Conclusion : Treatment of lung adenocarcinoma has changed thanks to the
identification of mutations like EGFR and EML4-ALK. The NCI’s Lung Cancer
Mutation Consortium (LCMC) has as goal to provide mutations results to clinicians
and to encourage them to provide erlotinib to patients with EGFR mutations and to
enter patients in clinical trials of targeted agents in lung cancer specimens and to
encourage clinicians.
Comment : We believe that such initiatives are very important to promote personalized
treatment of lung cancer. This might be the model for comparable facilities in order to
provide the opportunity of larger proportions of patients to be treated according to the
characteristics of the tumor they are suffering. However, a prerequisite is the
availability of the drugs patients are needing.
The ability to detect driver mutations like EGFR and EML4-ALK in tumor specimens from
patients with lung cancer and administer agents targeting those molecular lesions has
revolutionized the management of adenocarcinoma of the lung.The LCMC was created to
determine 10 driver mutations in tumors from 1,000 patients and to give the results to
clinicians for care and entry onto targeted therapeutic trials based on these findings. The 14
member LCMC is prospectively enrolling patients to test tumors from patients with lung
adenocarcinoma in CLIA laboratories for KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1,
MEK1, and NRAS using standard multiplexed assays and fluorescence in situ hybridization
(FISH) for ALK rearrangements and MET amplifications. All are stage IIIB/IV, PS 0-2, have
available tissue, and signed consent. 830 patients have been registered. with 50 enrolling
monthly. We detected a driver mutation in 60% (252/422, 95% CI 55 to 65%) of tumors thus
far. Mutations found: KRAS 107 (25%, 95% CI 21 to 30%), EGFR 98 (23%, 95% CI 19 to
27%), ALK rearrangements 14 (6%, 95% CI 4 to11%), BRAF 12 (3%, 95% CI 1 to 5%),
PIK3CA 11 (3%, 95% CI 1 to 5%), MET amplifications 4 (2%, 95% CI 0.5 to 5%), HER2 3,
(1%, 95% CI 0.1 to 2%), MEK1 2 (0.4%, 95% CI 0.1 to 2%), NRAS 1 (0.2%, 95% CI 0.01 to
1%), AKT1 0 (0%, 95% CI 0 to 1%). 95% of molecular lesions were mutually exclusive.