[JM Article 2] Amivantamab plus chemo tied to better outcomes vs chemo alone in advanced NSCLC

Treatment with amivantamab (ami) in combination with chemotherapy (chemo) results in substantially longer time to treatment discontinuation (TTD), time to subsequent therapy (TTST), and progression-free survival (PFS) after first subsequent therapy (PFS2) in patients with EGFR-mutant advanced nonsmall cell lung cancer (NSCLC) following progression on osimertinib, as shown in a postprogression analysis.

Ami, an EGFR-MET bispecific antibody with immune cell-directing activity, plus carboplatin-pemetrexed has been shown to extend PFS versus chemo alone in the MARIPOSA-2 study, said lead author Ryan D Gentzler, University Hospital of Virginia, Charlottesville, US, who presented the results of the current analysis at ELCC 2024. [Cancer Res 2016;76:3942-3953; Cancer Discov 2020;10:1194-1209]

“Amivantamab-chemotherapy represents the new standard of care among patients with EGFR-mutant advanced NSCLC after disease progression on osimertinib,” he said.

In MARIPOSA-2, a total of 657 patients with NSCLC were randomly assigned to receive either ami-chemo or chemo alone. The postprogression analyses centred on 131 patients who received ami-chemo (safety: n=130) and 263 treated with chemo alone (safety: n=243). Gentzler and his team modified a third arm (ami-lazertinib-chemo), but the results are yet to be obtained.

Disease progression occurred in 55 of 130 (42 percent) patients in the ami-chemo arm and 173 of 243 (71 percent) of those in the chemo alone arm over a median follow-up of 8.7 months.

Among patients with progressive disease, 19 of 55 (35 percent) in the ami-chemo arm and 28 of 173 (16 percent) in the chemo alone arm received treatment beyond progression for >4 weeks, with a median postprogression treatment duration of 18.3 and 9.0 weeks, respectively. [ELCC 2024, abstract 3MO]

Ami-chemo, compared with chemo alone, brought about a considerably extended TTD (median, 11.0 vs 4.5 months; hazard ratio [HR], 0.37, 95 percent confidence interval [CI], 0.28‒0.50; p<0.0001), TTST (median, 12.1 vs 6.6 months; HR, 0.42, 95 percent CI, 0.30‒0.59; p<0.0001), and PFS2 (median, 13.9 vs 11.3 months; HR, 0.60, 95 percent CI, 0.40‒0.92; p=0.017).

“Compared to chemotherapy [alone], amivantamab-chemotherapy in patients with EGFR-mutant advanced NSCLC after disease progression on osimertinib significantly prolonged [TTD, TTST, and PFS2],” Gentzler said.

Among participants who had progressive disease, including those treated beyond disease progression, 41 of 55 (75 percent) patients in the ami-chemo arm ceased treatment following progression compared to 161 of 173 (93 percent) of those in the chemo alone arm.

On the other hand, 63 percent of patients with progressive disease commenced subsequent systemic therapy in both groups. The most frequent subsequent therapies used were osimertinib (ami-chemo: 10 percent; chemo alone: 9 percent) and docetaxel (ami-chemo: 7 percent; chemo alone: 9 percent).

“Subsequent therapies received were similar in both arms, with osimertinib and docetaxel being the most common,” Gentzler said.

In terms of safety, “[t]he higher incidence and severity of haematologic adverse events for amivantamab-chemotherapy was limited to cycle 1, with profiles similar between both arms from cycle 2 onward,” he said.