Monotherapy For NSCLC

Afatinib Demonstrate Encouraging Efficacy As Well As
Safety in Late Stage EGFR-Mutant NSCLC
According to final outcomes of the ASCENT trial, which was came out during the International
Association for the Study of Lung Cancer 2021 Targeted Therapies of Lung Cancer Meeting,
“Integrating afatinib (Gilotrif) into standard-of-care chemoradiation either with or without surgery
showed the encouraging efficacy, feasibility, and safety outcomes in patients with stage-III EGFR
mutation +Ve NSCLC.”
Importance of neoadjuvant EGFR TKIs, and adjuvant EGFR TKIs in unresectable cancer, remains
unspecified, although outcomes from the ADAURA trial demonstrated that disease free survival in
patients with stage IB to IIIA EGFR mutation +Ve non-small cell lung cancer was specificallly longer in
patients who were given osimertinib than in those who were given placebo.
According to Andrew John Piper-Vallillo, MD, presenting author and clinical fellow in the hematology
or oncology at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston,
Massachusetts, ‘At the time of undergoing design of ASCENT trial, there were no findings for the
EGFR TKIs in stage-III non-small cell lung cancer.
In ASCENT, patients were given afatinib 40mg once daily for a couple of months and then underwent
restaging based on the primary end point assessment, ORR.
Patients then were given chemoradiation therapy (60 to 72 Gy) and concurrent cisplatin at 75
mg/m2 and pemetrexed at 500 mg/m2 every 3 weeks for up to 4-cycles, or induction
chemoradiation consist of neoadjuvant radiation therapy (45-54 Gy) and concurrent cisplatin and
pemetrexed for a couple of cycles and surgical resection.
In case there was no proof of the progressive disease, patients then were given adjuvant afatinib for
a couple of years. Surgery involved lobectomy/pneumonectomy. Secondary end points were PFS,
OS, and safety.
Afatinib specifically is a pan-ERBB TKI indicated in order to treat advanced EGFR mutation +Ve Non-
Small Cell Lung Cancer.
The approval came into action on behalf of the demonstration of durable responses in the subset of
the 32 afatinib treated patients with the metastatic non-small cell lung cancer whose tumors harbor
nonresistant epidermal growth factor receptor mutations enrolled in one of three clinical trials.
The study carried out for a total of 30 patients, but closed for slow accrual in 2020, enrolling 19
patients in between September 2012 and January 2020.
The median age was noted as 56 years (range, 34 to 75) with an enrolled total of 14 female patients.
12 (63%) patients were determined in order to have exon-19 deletion and 9 (37%) patients had the
L858R-mutation.
68 percent of patients were white or of 32 percent were Asian descent. 53% were never smokers,
and entire patients had adenocarcinoma. Of the nineteen participants, ten underwent resection.
Resectability was specified at diagnosis following the multidisciplinary team discussion, per protocol,
Piper-Vallillo stated.
According to Piper-Vallillo said, “Objective response rate was 58-percent specified following a couple
months of treatment along with the neoadjuvant afatinib.”
“Of the 9-patients with unresectable cancer who done with neoadjuvant therapy, single patient
progressed, single patient converted to the operable, seven patients proceeded to the definitive
chemoradiotherapy,” he added.
In unresectable patients and were given the definitive chemotherapy, one patient declined in order
to take adjuvant afatinib. Six patients were given adjuvant afatinib for a couple of years.
In the arm of resectable, ten patients were given neoadjuvant chemoradiotherapy as well as surgery.
In this subgroup, the dose of median radiotherapy was 54 Gy and patients underwent a couple of
median chemotherapy cycles. 10-patients underwent surgical resection, and 7-patients had a major
pathology response. 3-patients declined the adjuvant afatinib.
Totally 13-patients from both the arms were given adjuvant afatinib with a median duration of 22.4
months, excluding 4-patients who remained on the therapy. 5-patients done the specified a couple
of years of therapy, three patients discontinued a bit early, 1-patient had the recurrent disease
during adjuvant afatinib, and 4 pateints remain on the adjuvant therapy.
In the intention-to-treat group (n = 19), the median progression free survival was 34.6 months (95%
CI, 16.9 to 66.1), median overall survival was noted as 69.1 months (95% CI, 29.4 not releasable), and
the two year overall survival rate was noted as 88 percent (95% CI, 59% to 97%).
Further findings measures showed a recurrent tumor in 9 of 19-patients (47%), CNS-only recurrence
in 5 of 9-patients (55%), recurrence post-surgery in 3 of 10-patients (30%), and recurrence post
chemoradiotherapy in 5 of 7-patients (71%).
Regarding safety, 47 percent (9 of 19) of patients needed the dose of neoadjuvant afatinib reduction
from 40mg to 30mg, and one patient had a perisurgical side effect, which was atrial fibrillation that
needed the treatment.
38 % (5 of 13) of patients needed the adjuvant dose reduction from afatinib 40mg to afatinib 30mg
or afatinib 30mg to afatinib 20mg. An additional 23 percent (3 of 13) interrupted the adjuvant
afatinib due to the toxicity.
Notable grade-3/4 side effects included 6-patients with rash, 5-patients with diarrhea, 3-patients
with esophagitis, and 3-patients with nausea. 2-patients have grade-2 pneumonitis during
chemoradiotherapy or adjuvant afatinib. There were no treatment-related deaths.
Results from this integration of afatinib with standard of care chemoradiation, along with the
interim results of ADAURA, support the use of genotype-directed therapies in stage III EGFR-mutant
NSCLC, although the optimal sequence of TKI therapy needs to be defined, Piper-Vallillo said.
Because this trial was closed due to slow accrual, future studies will require multicenter
participation, he said.
Source: https://ikrispharma.wordpress.com/2021/04/16/afatinib-
demonstrate-encouraging-efficacy-as-well-as-safety-in-late-stage-egfr-
mutant-nsclc/

Monotherapy For NSCLC

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Monotherapy For NSCLC

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Afatinib Demonstrate Encouraging Efficacy As Well As

Safety in Late Stage EGFR-Mutant NSCLC

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