Dr Raffaele Califano is Consultant in Medical Oncology at The Christie and University Hospital of South Manchester, Manchester, UK.


CALIFANO ASCO

"This [is] an analysis of the progression-free survival [stratified] by molecular aberration, which represents the mechanism of resistance post-osimertinib [in] all patients who were enrolled in the MARIPOSA-2 study. The data [show] is that chemotherapy plus amivantamab is an effective regimen, regardless of the baseline mechanism of resistance post-[osimertinib], and therefore it remains a standard of care in this setting."

Raffaele Califano, MD, a consultant in medical oncology at the Christie and Manchester University Hospital, detailed outcomes based on baseline resistance mechanisms in the phase 3 MARIPOSA-2 trial (NCT04988295), which evaluated amivantamab-vmjw (Rybrevant) in combination with chemotherapy vs chemotherapy alone in patients with advanced 

-mutant non–small cell lung cancer (NSCLC) following disease progression on osimertinib (Tagrisso).

The trial enrolled patients with advanced NSCLC harboring 

 exon 19 deletions or exon 21 L858R substitution mutations whose disease progressed on osimertinib. Baseline circulating tumor DNA (ctDNA) was collected and analyzed using the Guardant360 and FoundationOne CDx platforms to identify putative resistance mechanisms to osimertinib.

Findings from an analysis of outcomes based on osimertinib resistance mechanisms, which were presented at the 

, showed that amivantamab plus chemotherapy improved PFS in patients with detectable ctDNA at baseline (HR, 0.49; 95% CI, 0.36-0.68; 

 comutations (HR, 0.63; 95% CI, 0.44-0.92; 

PFS was also improved with the combination in patients with 

 independent resistance mechanisms (HR, 0.54; 95% CI, 0.31-0.94; 

 = .025), dependent resistance mechanisms (HR, 0.57; 95% CI, 0.33-0.99; P = .042), and unknown resistance mechanisms (HR, 0.31; 95% CI, 0.17-0.56; 

 secondary mutations emerged as the most common resistance alterations. Califano noted that across all molecular subgroups, the combination of amivantamab plus chemotherapy demonstrated superior progression-free survival (PFS) outcomes compared with chemotherapy alone.

Importantly, benefit from the amivantamab-based regimen extended beyond biomarker-defined populations, Califano explained. Patients with 

 co-mutations or unknown resistance mechanisms also experienced improved outcomes, suggesting a broad therapeutic impact regardless of the molecular driver of resistance.

These findings underscore the role of amivantamab plus chemotherapy as a standard-of-care regimen following progression on osimertinib, Califano said.

Videos

Raffaele Califano, MD, discusses molecularly stratified outcomes amivantamab with chemotherapy vs chemotherapy alone in patients with advanced EGFR-mutant NSCLC.

Dr Califano on MARIPOSA-2 Outcomes by Baseline Resistance Mechanisms in EGFR+ NSCLC

Raffaele Califano, MD, consultant in medical oncology at the Christie NHS Foundation Trust and University Hospital of South Manchester, discuses the potential for immunotherapy in small-cell lung cancer (SCLC).

Several studies have investigated checkpoint inhibitors in SCLC, says Califano. These include the Checkmate 032, which looked at nivolumab either alone or with ipilimumab. The single-agent nivolumab arm demonstrated an 18% response rate, says Califano. The disease-free survival rate was 54% for the combination arm.

Based on this data there are now trials ongoing looking at nivolomab as a second-line treatment in patients with small-cell lung cancer.

The checkpoint inhibitor pembrolizumab was also investigated in SCLC as a single agent in the Keynote-28 study. In this study, patients were selected based on PD-L1 expression, explains Califano. The overall response rate was 35%, high for this patient population, he says, and the drug was very well tolerated.

A number of other studies looking at pembrolizimab have been launched, which are investigating it as both a single-agent and a maintenance treatment. Immunotherapy offers significant promise for this patient population, which does not have many other treatment options, says Califano.

View more from the 2016 European Lung Cancer Conference

Raffaele Califano, MD

Articles

Dr Califano on MARIPOSA-2 Outcomes by Baseline Resistance Mechanisms in EGFR+ NSCLC

Dr. Raffaele Califano on Immunotherapy in Small-Cell Lung Cancer