ALK+ advanced non-small cell lung cancer: safety and clinical activity results from a study of Alectinib plus Atezolizumab
Alectinib ( Alecensa ) has proven systemic and CNS efficacy in patients with ALK+ aNSCLC ( advanced non-small cell lung cancer ) ( ALEX trial ). T
umor cell death caused by Alectinib may release antigens broadening the potential anti-tumor T cell response.
The monoclonal antibody Atezolizumab ( Tecentriq ) releases T cell suppression by inhibiting PD-L1 binding and improves overall survival ( OS ) in second-line NSCLC treatment.
Researchers have hypothesized Atezolizumab in combination with Alectinib would lead to enhanced efficacy.
A phase Ib enrolled treatment-naïve pts with ALK+ aNSCLC regardless of PD-L1 status, including patients with untreated asymptomatic brain metastases.
Patients received Alectinib 600 mg PO BID for 7 days ( safety evaluation) , followed by Alectinib 600 mg PO BID with Atezolizumab 1200 mg IV q3w ( expansion stage ) until progression or unacceptable toxicity.
The primary objective was to evaluate the safety and tolerability of the combination. Secondary objectives included evaluation of tumor response ( ORR ) per RECIST v1.1.
At cut-off ( 18 August 2017 ) 21 patients ( safety stage n = 7; expansion stage n = 14 ) who received greater than or equal to 1 dose of Alectinib or Atezolizumab were considered safety evaluable.
Median age was 53 years.
Incidence of grade 3 and serious adverse events were 62% ( 52.4% treatment-related ) and 33%, respectively.
No grade 4–5 adverse effects were reported.
Four patients ( 19% ) discontinued Atezolizumab and 2 patients ( 10% ) discontinued Alectinib due to adverse effects.
14 patients ( 67% ) had Alectinib dose interruptions / modifications.
No dose-limiting toxicities were observed.
At a median follow up of 13 months, ( 1–22 ), ORR was 81% ( 95% CI 58.1–94.6 ); median progression-free survival was 21.7 months ( 95% CI 10.3–21.7 ), median duration of response was 20.3 months ( 95% CI 11.5–20.3 ), however, only 6 pts had progressed at the time of data cut-off.
On-treatment CD8+ T-cell increase was observed post-Alectinib run-in.
in conclusion, the combination of full dose Alectinib and Atezolizumab appears to have an acceptable safety profile with no new safety findings for either agent.
Early efficacy results are encouraging but further follow-up is needed to define the role of this combination in patients with treatment-naïve ALK+ NSCLC. ( Xagena )
Source: American Society of Clinical Oncology - ASCO Meeting, 2018
Hyperprogressive disease in advanced non–small cell lung cancer patients treated with immune checkpoint inhibitors
Hyperprogressive disease ( HPD ) is a paradoxical boost in tumour growth described in a subset of cancer patients treated...
Pembrolizumab in combination with chemotherapy has improved overall survival versus chemotherapy alone as first-line treatment for patients with advanced NSCLC whose tumors do not express PD-L1
The first-line treatment with Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with chemotherapy has demonstrated improvements in overall...
FDA has warned about rare but severe lung inflammation with Ibrance, Kisqali, and Verzenio for breast cancer
The FDA ( U.S. Food and Drug Administration ) has warned that Ibrance ( Palbociclib ), Kisqali ( Ribociclib ),...
The European Commission has granted marketing authorization in the European Union ( EU ) for the precision oncology treatment Vitrakvi...
Ibrance: FDA has expanded approved use of metastatic breast cancer treatment to include male patients
The FDA ( U.S. Food and Drug Administration ) has extended the indication of Ibrance ( Palbociclib ) capsules in...
FDA has approved Piqray, the first PI3K inhibitor for HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer
The FDA ( U.S. Food and Drug Administration ) has approved Piqray ( Alpelisib ) tablets, to be used in...
Lorviqua for treatment of adult patients with ALK-positive advanced non-small cell lung cancer, previously treated with one or more ALK tyrosine kinase inhibitors: approved in European Union
The European Commission ( EC ) has granted conditional marketing authorization for Lorviqua ( Lorlatinib, available in the U.S., Canada...
Talzenna, a PARP inhibitor, approved in European Union for germline BRCA-mutated locally advanced or metastatic breast cancer
The European Commission has approved Talzenna ( Talazoparib ), an oral poly (ADP-ribose) polymerase ( PARP ) inhibitor, as monotherapy...
The results of a study has shown that patients living with HIV and one of a variety of potentially deadly...
Nivolumab plus Ipilimumab - Combination checkpoint blockade effective in pre-surgical setting for early-stage lung cancers
Neoadjuvant, or pre-surgical, treatment with Nivolumab ( Opdivo ) plus Ipilimumab ( Yervoy ) resulted in an overall major pathologic...