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.
Note:- This Information is first published here
