ABSTRACT
Background: Durable clinical benefit has been achieved with nivolumab (NIVO) + ipilimumab (IPI), including an overall survival (OS) of 49% and a melanoma-specific survival (MSS) of 56%, with median MSS not reached (NR) at 6.5-y minimum follow-up. Here we report sustained efficacy outcomes at 7.5 y. Methods: Patients (pts) with previously untreated, unresectable stage III/IV melanoma were randomly assigned 1:1:1 and stratified by PD-L1 status, BRAF mutation status, and metastasis stage to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W, followed by NIVO 3 mg/kg Q2W (n = 314);NIVO 3 mg/kg Q2W + placebo (n = 316);or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were progression-free survival (PFS) and OS with NIVO + IPI or NIVO alone versus IPI. Results: With a minimum follow-up of 7.5 y, median OS remained stable at 72.1 mo (NIVO + IPI), 36.9 mo (NIVO), and 19.9 mo (IPI);median MSS was NR, 49.4 mo, and 21.9 mo, respectively (Table). While the objective response rate remained stable at 58% (NIVO + IPI), 45% (NIVO), and 19% (IPI), median duration of response had now been reached for NIVO at 90.8 mo and remains NR and 19.2 mo for NIVO + IPI and IPI, respectively. Subsequent systemic therapy was received by 36%, 49%, and 66% of NIVO + IPI-, NIVO-, and IPI-treated patients, respectively, and median time to that therapy was NR (95% CI, 45.9-NR), 24.7 mo (16.0-38.7), and 8.0 mo (6.5-8.7). Of patients alive at 7.5 y, 106/138 (77%, NIVO + IPI), 80/115 (70%, NIVO), and 27/60 (45%, IPI) were off treatment and had never received subsequent systemic therapy. No change to the safety summary was observed with additional follow-up;updated health-related quality of life data will be reported. Of the 10 new deaths since the 6.5-y follow-up (ie, 5 NIVO + IPI;3 NIVO;2 IPI), none were treatment-related;4 were due to melanoma progression;1 was due to an unknown cause;and 5 were due to other causes, but not associated with a COVID diagnosis. Conclusions: The 7.5-y follow-up continues to demonstrate the durability of responses with NIVO + IPI and an ongoing survival plateau. A substantial difference in median OS and MSS between patients treated with NIVO + IPI or NIVO was observed in descriptive analyses.
ABSTRACT
Background: Patients with lung cancers may have distinct vulnerability to severe COVID-19. Understanding thepatient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer careduring this pandemic. A key question is whether PD-1 blockade therapy impacts COVID-19 severity. Methods: We identified consecutive patients with lung cancer and a positive SARS-CoV-2 RT-PCR test seen at asingle cancer center in New York City. We performed detailed manual review of the disease course, medical andoncologic history. COVID-19 severity outcomes were predefined, including need for hospitalization, ICU/intubation/transition to DNI-status, or death. We examined clinical features associated with severity using singleand multivariable analyses. Regarding the impact of PD-1 blockade, we prespecified several bio-plausiblecomparisons of PD-1 exposure. HLA alleles were inferred from NGS and compared to controls with lung cancer andno known COVID-19. Results: We identified 102 patients with lung cancers and a SARS-CoV-2 positive swab between March 12, 2020and May 6, 2020. Patients were followed until May 11, 2020. COVID-19 was severe in patients with lung cancers(62% hospitalized, 25% died), but accounted for only 11% of deaths among patients with lung cancer during thepandemic. Determinants of COVID-19 severity were largely patient specific, including smoking status and chronicobstructivesystemic therapies, did not impact severity. Likelihood of severe COVID-19 was generally similar across HLA class Isupertypes. We found no significant differences in the impact of PD-1 blockade on COVID-19 severity. Modestnumerical increases in severity of COVID-19 associated with prior PD-1 blockade were diminished (Odds ratio 0.86-1.01) after adjusting for expected imbalances in prior smoking history. Most patients recovered from COVID-19, including 25% of patients initially requiring intubation. Conclusion: COVID-19 is associated with a high burden of severity in patients with lung cancers. Patient-specificfeatures, rather than cancer-specific features or treatments, were the greatest determinants of severity. In particular, PD-1 blockade did not appear to impact severity of COVID-19 in patients with lung cancers.