Annual Meeting Proceedings Part 1 - American Society of Clinical ...

7571 General Poster Session (Board #48E), Sat, 1:15 PM-5:15 PM
Phase II study of amrubicin (AMR) for patients (pts) with non-small cell
lung cancer (NSCLC) as third-line or fourth-line chemotherapy: Hokkaido
Lung Cancer Clinical Study Group trial (HOT) 0901. Presenting Author:
Toshiyuki Harada, Hokkaido Social Insurance Hospital, Sapporo, Japan
Background: Although an increasing number of NSCLC pts receive thirdline
chemotherapy with the established benefit of second-line chemotherapy,
the role of cytotoxic agent in this setting has not yet been well
defined prospectively. AMR, third-generation synthetic anthracycline agent,
has found favorable clinical activity and acceptable toxicity for NSCLC as
well as small cell lung cancer. This prospective trial was conducted to
evaluate the efficacy and safety of AMR for NSCLC pts as third-line or
fourth-line chemotherapy. Methods: Eligible pts had a performance status 0
to 2, failure of second-line or third-line chemotherapy, and adequate organ
function. Pts received AMR 35 mg/m2 intravenously on days 1-3 every 3
weeks. The primary endpoint was disease control rate (DCR: CR � PR �
SD). Secondary endpoints were overall survival (OS), progression-free
survival (PFS), response rate (CR � PR), and toxicity profile. The estimated
accrual was 37 pts to confirm a DCR of 50% as desirable target level and a
DCR of 30 % as uninteresting with alpha � 0.05 and beta � 0.20. Results:
From August 2009 to May 2011, 41 pts were enrolled from 10 institutions.
Patient characteristics were: male/female 29/12; median age 66 (range
43–74); performance status 0/1/2 16/24/1; adenocarcinoma/squamous
cell carcinoma/large cell carcinoma/not other specified 30/8/2/1; EGFR
mutation positive/negative/unknown 7/26/8; treatment lines 3rd/4th 26/
15. The median number of treatment cycles was 2 (range 1-9). The
objective responses were CR 0, PR 4, SD 22, PD 14, and NE 1, giving a
DCR of 61.0% (95% CI, 46.0-75.9%). Overall response rate was 9.8%
(95% CI, 0.6-18.8%). Median PFS was 2.6 months, whereas median
survival time was not reached. Grade 3/4 hematological toxicities were
neutropenia (68%), anemia (12%), thrombocytopenia (12%), and febrile
neutropenia (17%). Grade 3/4 non-hematological toxicities were anorexia
(12%), nausea (10%), and pneumonitis (2%). No treatment-related death
was observed. Conclusions: AMR shows significant clinical activity with
acceptable toxicities as third-line or fourth-line chemotherapyfor advanced
NSCLC.
7573 General Poster Session (Board #48G), Sat, 1:15 PM-5:15 PM
Cutaneous toxicity secondary to erlotinib therapy in patients with non-small
cell lung cancer in the NCIC CTG BR.21 study: Time course and correlation
with survival. Presenting Author: Roman Perez-Soler, Montefiore Medical
Center/Albert Einstein College of Medicine, Bronx, NY
Background: Cutaneous rash often develops in erlotinib-treated patients
(pts) and is thought to be associated with improved response and survival.
This analysis focuses on incidence, severity, and time course of skin rash
secondary to erlotinib, as well as the correlation between rash development
and overall survival (OS) in pts in the NCIC CTG BR.21 (NCT00036647)
trial. Methods: Pts with stage IIIB or IV non–small cell lung cancer (NSCLC)
who had failed first- or second-line chemotherapy were randomized 2:1 to
erlotinib or placebo. Cutaneous toxicity was graded per NCI CTC v2.0 and
managed at the discretion of the treating investigator. This retrospective
analysis used a landmark approach, dividing pts into rash and no-rash
groups, by the appearance of rash by week 10. Results: A total of 366 of
488 erlotinib-treated pts (75%) and 40 of 243 placebo-treated pts (16%)
developed rash at any time point. Of the former, 75% of rash episodes
occurred by week 2. The incidence of grades 1 and 2 rash peaked at week
3; grade 3 rash peaked at week 5. The erlotinib dose was reduced in 48 pts
(10%) due to rash. In most erlotinib-treated pts with rash, severity
decreased or plateaued over time (Table). Some 311 erlotinib-treated pts
(rash group) developed rash by week 10. Median OS in the erlotinib-treated
rash (n�311) and no-rash (n�65) groups were 37.4 and 11.1 weeks,
respectively (hazard ratio�0.51 [95% confidence interval, 0.38–0.68];
P�.0001). Baseline factors significantly associated with prolonged OS in
the rash population included race (Asian vs white), number of affected
organs (�3 vs�3), and smoking status (never vs ever). Conclusions: For
most pts, rash secondary to erlotinib presented within the first 2 weeks,
peaked during weeks 3–5, decreased thereafter, and did not necessitate
dose reduction, thus supporting SATURN results (Perez-Soler, ASCO
2011, abst. 7610). Development of rash by week 10 of erlotinib therapy
was associated with significantly improved OS.
Initial grade n*
Lesser
Grade at last assessment, no. (%)
Same Greater
1 207 – 175 (85) 32 (15)
2 125 51 (41) 71 (57) 3 (2)
3 19 12 (63) 6 (32) 1 (5)
4 2 0 (0) 2 (100) 0 (0)
* Of 353 pts with rash grade levels evaluated over time.
Lung Cancer—Non-small Cell Metastatic
497s
7572 General Poster Session (Board #48F), Sat, 1:15 PM-5:15 PM
Treatment with EGFR tyrosine kinase inhibitors beyond progression in
long-term responders to erlotinib in advanced non-small cell lung cancer: A
case-control study of overall survival. Presenting Author: Martin Faehling,
Klinik für Kardiologie und Pneumologie, Klinikum Esslingen, Esslingen,
Germany
Background: EGFR-tyrosine kinase inhibitor (TKI) such as erlotinib lead to
prolonged disease stabilization in some patients with advanced NSCLC. It
is so far not clear how to treat patients who progress after prolonged
response to erlotinib. TKI therapy beyond progression with added chemotherapy,
radiotherapy or best supportive care (BSC) may improve survival
compared to chemotherapy, radiotherapy or BSC alone. Methods: We
retrospectively analyzed all NSCLC patients treated with erlotinib at our
institutions since 2004 who progressed after at least stable disease on
erlotinib for at least six months (n�41). Twenty-seven patients were
treated with TKI beyond progression (TKI patients), of whom 24 received
erlotinib and 3 afatinib. Fourteen patients did not receive further TKI
treatment after progression (controls). Overall survival (OS) from progression
on TKI and OS from diagnosis of lung cancer was analyzed for the
whole population and case-control subpopulations of pairs matched for
gender, smoking status, and histology. Results: Treatment with TKI and
chemotherapy was well tolerated with no increase in grade 3 and 4
toxicities. TKI-patients had a significantly longer OS from progression on
TKI (case control: median 21.0 vs. 3.0 months, HR 0.175) and longer OS
from diagnosis of lung cancer (case control: median 28.5 vs. 15.3 months,
HR 0.335). Conclusions: In long-term erlotinib responders, treatment with
TKI beyond progression in addition to chemotherapy or radiotherapy is
feasible and well tolerated with limited toxicity. TKI-treatment beyond
progression improved OS compared to treatment with TKI-free chemotherapy
or radiotherapy.
7574 General Poster Session (Board #48H), Sat, 1:15 PM-5:15 PM
Efficacy of pemetrexed as second-line therapy in advanced NSCLC after
either treatment-free interval or maintenance therapy with gemcitabine or
erlotinib in IFCT-GFPC 05-02 phase III study. Presenting Author: Olivier
Bylicki, Hospices Civils de Lyon, Lyon, France
Background: Continuous exposure of tumor cells to maintenance therapy in
advanced NSCLC might lead to resistance to subsequent treatments.
IFCT–GFPC 0502 study showed a progression-free survival (PFS) benefit
with gemcitabine (G) or erlotinib (E) maintenance compared to observation
(O) after cisplatin-G induction chemotherapy. The trial included a predefined
second-line therapy with pemetrexed (P), allowing post-hoc assessment
of its efficacy according to previous maintenance treatment or
treatment-free interval. Methods: Stage IIIB/IV NSCLC patients (pts) with a
PS of 0-1 were randomized after 4 cycles of cisplatin-G chemotherapy to O
or to receive maintenance therapy with G or E until disease progression. P
was given as second-line treatment on disease progression in all arms. PFS
and OS were assessed from the beginning of P therapy according to
randomization arm. Tumor response to P and tolerance were also analyzed.
Results: Of the 464 pts randomized to either O (155), G (154) or E (155),
360 pts (78 %) received P as second-line therapy, i.e. 130 (84%), 114
(74%) and 116 (75%) in O, G and E arm, respectively. Baseline
characteristics remained well balanced between arms (overall median age
of 58 years, 28% female, 91% stage IV, 41% PS 0, 65/19/16%,
adenocarcinoma/squamous/other, 10% non-smokers and 56% responders
to induction CT). Median number of delivered P cycles was 3 (1-40) in all
arms. Response rate was 19%, 7% and 15% for non-squamous pts in O, G
and E, respectively. Median PFS did not significantly differ between G and
O (4.2 vs 3.9 months, HR [95% CI] 0.81 [0.62-1.06]) or E and O (4.2 vs
3.9 months, HR 0.83 [0.64-1.09]). OS data showed a non-significant
improvement with G vs O (HR 0.81 [0.61-1.07]) or E vs O (HR 0.80
[0.61-1.05]), with a median of 7.5, 8.3 and 9.1 months for O, G and E,
respectively. Results were similar when analysis was restricted to nonsquamous
pts. Grade 3-4 treatment-related AEs were similar in O (33.1%),
G (31.6%) and E (25%). Conclusions: Maintenance therapy with continuation
of G or switch to E does not impair the efficacy of second-line P by
comparison with administration after a treatment-free interval.
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