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Amivantamab Plus Chemotherapy Improved Post-Progression Outcomes Among Patients With Advanced EGFR-Mutated Non-Small Cell Lung Cancer
Joshua Sabari, MD, NYU Langone Health, New York, New York, discussed post-progression secondary end points from the phase 3 PAPILLON trial, as presented at the European Lung Cancer Congress 2024.
Results demonstrated that amivantamab plus chemotherapy significantly prolonged time to treatment discontinuation and time to subsequent therapy among patients with advanced, EGFR ex20ins-mutated non-small cell lung cancer (NSCLC). Dr Sabari noted this regimen should be considered the new first-line standard of care.
Transcript:
Hello, I'm Dr Joshua Sabari, Thoracic Medical Oncology at NYU Langone Health, Perlmutter Cancer Center in New York, and it was really an exciting European Lung Cancer Congress (ELCC) 2024, where we saw many updates in thoracic malignancies. I want to first focus on an abstract titled amivantamab plus chemotherapy versus chemotherapy as first-line treatment in EGFR ex20ins-mutated advanced non-small cell lung cancer. This is an analysis of the post-progression end points from PAPILLON, and I was fortunate to be an author and a steering member committee on this investigation.
This is studying a novel combination strategy in patients with EGFR ex20ins-mutant lung cancer in the front-line setting. If you remember from the CHRYSALIS data, we saw impressive response rates of 40%, we saw progression-free survival of 8.3 months in the second-line setting, leading to an accelerated approval of amivantamab, an EGFR and c-MET bispecific antibody, in patients with EGFR ex20ins-mutant non-small cell lung cancer. Here we take that agent, amivantamab, and we combine it with chemotherapy in the front-line setting in an effort to move and utilize this therapeutic option for patients in the front-line setting.
The PAPILLON trial is a randomized, phase 3 study, international global trial, enrolled over 300 patients randomized 1-to-1 to receive amivantamab plus chemotherapy versus chemotherapy alone. The primary end point here was median progression-free survival by blinded independent central review. We also looked at some key secondary end points: response rate, duration of response, and survival. Here in this abstract we’re going to discuss time-to-second treatment and we’ll also look at some of the exploratory end points of time-to-treatment discontinuation. Remember, this was a randomized trial and patients who were randomized to receive the control arm, chemotherapy alone, were allowed to cross over to second-line amivantamab monotherapy and we’ll talk about that data as well. We know that 2/3 (66%) of patients rolled over to receive amivantamab. The primary end point for this trial presented back at ESMO was the progression-free survival, a hazard ratio here of 0.4, so if you received amivantamab plus chemotherapy, median progression-free survival 11.4 months versus chemotherapy alone of 6.7 months. This led to the FDA approval of this regimen in the front-line setting.
What was exciting to see at this past conference was time-to-treatment discontinuation. We know that median time-to-treatment discontinuation was significantly longer with amivantamab plus chemotherapy compared to chemotherapy alone with a hazard ratio here of 0.38. Your time-to-treatment discontinuation, 35% of patients remained on therapy with amivantamab and chemotherpy at 18 months versus only 5% of those who received chemotherapy alone. When we look at some of the sites of progression of disease, what really stood out to me was that there is almost a doubling of improvement in the CNS progression rate. Only about 5.2% of patients progressed in the CNS who received amivantamab and chemotherapy versus about 9% who received chemotherapy alone. When we look at time-to-subsequent therapy, median time-to-subsequent therapy was significantly longer with amivantamab and chemotherapy compared to chemotherapy, hazard ratio here of 0.35 with a median time-to-subsequent therapy of 17.7 months for amivantamab and chemotherapy and only 9.9 months for chemotherapy alone. So, what were the common subsequent therapies? If you received amivantamab and chemotherapy, most patients went on to get systemic therapy with chemotherapy alone. If you received chemotherapy in the front-line, most patients did go on to receive amivantamab in the second-line setting. What I think was interesting about this abstract was that we looked at that crossover, second-line patient population receiving amivantamab, they’re getting the Q3 week regimen, we’re used to the Q2 week regimen, and really no significant differences here. Median progression-free survival 6.8 months, median overall survival 17.7 months for that control arm who crossed over, very similar to what we have seen in the CHRYSALIS cohort D study.
In conclusion, compared to chemotherapy, amivantamab plus chemotherapy, which is the new standard front-line regimen for patients with EGFR ex20ins-mutant disease, prolonged both time-to-treatment discontinuation, 13.2 months for the treatment arm versus 7.5 months and also improved the time-to-subsequent therapy, 17.7 months for the treatment arm and 9.9 months for the control arm. I think what was helpful to see was in the control arm, those patients who received chemotherapy alone and then crossed over to receive amivantamab, there was really no significant difference cross trial comparison of the Q3 week regimen versus that Q2 week regimen.
Amivantamab and chemotherapy based on the PAPILLON data is the new first-line standard of care for patients with ex20ins-mutant disease and was fully approved in the front-line setting March 1st, 2024.
Source:
Felip E, Zhou C, Tang KJ, et al. Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced NSCLC: Analysis of post-progression endpoints from PAPILLON. Presented at the European Lung Cancer Congress 2024; March 20-23, 2024. Prague, Czech Republic. Abstract 2MO
