OBJECTIVE: To evaluate the effect of different phytohormones on callus induction, subculture cycle, and regeneration studies of callus in C. borivilianum.

MATERIALS AND METHODS: Young shoot buds of C. borivilianum were inoculated on Murashige and Skoog medium fortified with 3% sucrose and different concentrations (0, 1, 5, 10, and 15 mg/L) of either naphthalene acetic acid or 2,4-dichlorophenoxyacetic acid or indole-3-acetic acid and callus induction was evaluated up to four subcultures cycles. Shoot regeneration from callus was studied on Murashige and Skoog media fortified with 6-benzylaminopurine andkinetin or thidiazuron at varied levels (0, 0.5, 1, 2, and 3 mg/L). Microshoots were rooted on Murashige and Skoog media supplemented with 1.0 mg/L indole-3-butyric acid and plantlets were acclimatized before transferred to the natural conditions.

RESULTS: Callus induction was better evidenced on Murashige and Skoog media containing 5 mg/L 2,4-dichlorophenoxyacetic acid up to fourth subculture. Callus differentiated into shoots on Murashige and Skoog media fortified with 6-benzylaminopurine or kinetin, whereas thidiazuron completely failed to regenerate shoots. Furthermore, microshoots rooted on 1.0 mg/L indole-3-butyric acid containing Murashige and Skoog media. The rooted plantlets were successfully acclimatized and established in soil with 88.3% survivability.

CONCLUSION: The type of auxins played an important role in inducing callus tissue from shoot bud explants of Safed musli. In future, this in vitro protocol could benefit in crop improvement programs and serve as a new source of bioactive compounds from Safed musli callus tissue for various therapeutic applications.

METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours.

RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported.

PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion.

RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy.