{"id":48218,"date":"2022-09-11T15:01:37","date_gmt":"2022-09-11T13:01:37","guid":{"rendered":"https:\/\/pharma-trend.com\/en\/imfinzi-durvalumab-and-tremelimumab-with-chemotherapy-demonstrated-sustained-survival-benefit-in-metastatic-non-small-cell-lung-cancer-nearly-doubling-the-number-of-patients-alive-after-three\/"},"modified":"2022-09-11T15:01:37","modified_gmt":"2022-09-11T13:01:37","slug":"imfinzi-durvalumab-and-tremelimumab-with-chemotherapy-demonstrated-sustained-survival-benefit-in-metastatic-non-small-cell-lung-cancer-nearly-doubling-the-number-of-patients-alive-after-three","status":"publish","type":"post","link":"https:\/\/pharma-trend.com\/en\/imfinzi-durvalumab-and-tremelimumab-with-chemotherapy-demonstrated-sustained-survival-benefit-in-metastatic-non-small-cell-lung-cancer-nearly-doubling-the-number-of-patients-alive-after-three\/","title":{"rendered":"IMFINZI\u00ae (durvalumab) and tremelimumab with chemotherapy demonstrated sustained survival benefit in metastatic non-small cell lung cancer, nearly doubling the number of patients alive after three years vs. chemotherapy"},"content":{"rendered":"
\n

\nExploratory analysis from POSEIDON Phase III trial also showed trends for overall survival benefit with a limited course of tremelimumab added to IMFINZI and chemotherapy in subgroups with high unmet need<\/i><\/b>\n<\/p>\n

WILMINGTON, Del.–(BUSINESS WIRE)–Updated results after approximately four years of follow-up of the POSEIDON Phase III trial showed a limited course of tremelimumab when added to AstraZeneca\u2019s IMFINZI\u00ae<\/sup> (durvalumab) plus four cycles of chemotherapy demonstrated a sustained improvement in overall survival (OS) compared to chemotherapy alone in the 1st-line treatment of patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). Additional post-hoc, exploratory analyses continued to show a trend for OS improvement with this combination in patients with STK11, KEAP1 and KRAS-mutated NSCLC, as well as in patients whose tumors were PD-L1-negative (less than 1% tumor cell expression).\n<\/p>\n

<\/a><\/p>\n

\nThese late-breaking results were presented today at the European Society of Medical Oncology (ESMO) Congress 2022 (Abstract #LBA59).\n<\/p>\n

\nKRAS mutations are the most common tumor growth driver in NSCLC, occurring in approximately 25% of patients. NSCLC tumors with STK11 and KEAP1 mutations are often associated with poor outcomes and classified as immunologically \u201ccold.\u201d KRAS-mutated NSCLC can be responsive to immunotherapy but also can have poor outcomes, particularly when associated with STK11 or KEAP1 co-mutations.1-6<\/sup>\n<\/p>\n

\nMelissa Johnson, MD, Director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, and a lead investigator in the POSEIDON Phase III trial, said: “Metastatic non-small cell lung cancer is a devastating diagnosis, particularly for patients whose cancers are less responsive to standard treatments such as chemotherapy and immune therapy. These results support the addition of a limited course of tremelimumab to durvalumab plus chemotherapy as a potential new treatment option for patients with these harder-to-treat forms of lung cancer.\u201d\n<\/p>\n

\nSusan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These updated POSEIDON results at nearly four years of follow-up show further evidence that the addition of a limited course of tremelimumab to IMFINZI <\/i>plus chemotherapy improves outcomes for metastatic non-small cell lung cancer patients, including those with specific tumor mutations where a high unmet need for effective, well tolerated treatments remains. We look forward to bringing this potential new treatment option to patients as quickly as possible.”\n<\/p>\n

\nThese latest data show that a limited course of five cycles of tremelimumab added to IMFINZI plus platinum-based chemotherapy improved overall survival by 25% compared to chemotherapy alone (hazard ratio [HR] 0.75; 95% CI 0.63-0.88). Updated median OS was 14 months for the combination versus 11.7 for chemotherapy alone. An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone.\n<\/p>\n

\nA trend for OS improvement continued to be observed in patients with STK11<\/i>, KEAP1<\/i>, and KRAS<\/i>-mutated mNSCLC when treated with the combination, which reduced the risk of death by 38% (based on a HR of 0.62; 95% CI 0.34-1.12), 57% (based on a HR of 0.43; 95% CI 0.16-1.25), and 45% (based on a HR of 0.55; 95% CI 0.36-0.85), respectively. The combination also extended sustained OS benefit to patients with less than 1% PD-L1 tumor cell expression. These post hoc, exploratory subgroup analyses should be interpreted with caution due to the small sample sizes.\n<\/p>\n

\nConsistent with previous POSEIDON Phase III trial readouts, OS benefit in these updated results appeared more pronounced with tremelimumab plus IMFINZI and chemotherapy in patients with non-squamous NSCLC histology. A 32% improvement in OS compared to chemotherapy alone (HR 0.68; 95% CI 0.55\u20130.85) was reported for patients with non-squamous histology, with an updated median OS of 17.2 months for the combination versus 13.1 months for chemotherapy. An estimated 31.4% of patients with non-squamous NSCLC treated with the combination were alive at three years versus 17.3% for those receiving chemotherapy alone.\n<\/p>\n

\nSummary of efficacy resultsi, ii<\/sup><\/b>\n<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

\n\u00a0\n<\/p>\n<\/td>\n

\n

\nTremelimumab + <\/b>IMFINZI
+ chemotherapy<\/b>\n<\/p>\n<\/td>\n

\n

\nChemotherapy<\/b>\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nIntention-To-Treat (ITT)<\/b>\n<\/p>\n<\/td>\n

\n

\nn=338\n<\/p>\n<\/td>\n

\n

\nn=337\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nMedian OS (in months)\n<\/p>\n<\/td>\n

\n

\n14.0\n<\/p>\n<\/td>\n

\n

\n11.7\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nHazard ratio (95% CI)iii<\/sup>\n<\/p>\n<\/td>\n

\n

\n0.75 (0.63, 0.88)\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nOS rate at 3 years (%)\n<\/p>\n<\/td>\n

\n

\n25.0\n<\/p>\n<\/td>\n

\n

\n13.6\n<\/p>\n<\/td>\n<\/tr>\n

\n

\n\u00a0\n<\/p>\n<\/td>\n

\n

\n\u00a0\n<\/p>\n<\/td>\n

\n

\n\u00a0\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nSTK11 <\/i>mutation<\/b>\n<\/p>\n<\/td>\n

\n

\nn=31\n<\/p>\n<\/td>\n

\n

\nn=22\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nMedian OS (in months)\n<\/p>\n<\/td>\n

\n

\n15.0\n<\/p>\n<\/td>\n

\n

\n10.7\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nHazard ratio (95% CI)iv<\/sup>\n<\/p>\n<\/td>\n

\n

\n0.62 (0.34, 1.12)\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nOS rate at 3 years (%)\n<\/p>\n<\/td>\n

\n

\n25.8\n<\/p>\n<\/td>\n

\n

\n4.5\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nKEAP1 <\/i>mutation<\/b>\n<\/p>\n<\/td>\n

\n

\nn=22\n<\/p>\n<\/td>\n

\n

\nn=6\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nMedian OS (in months)\n<\/p>\n<\/td>\n

\n

\n13.7\n<\/p>\n<\/td>\n

\n

\n8.7\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nHazard ratio (95% CI)iv<\/sup>\n<\/p>\n<\/td>\n

\n

\n0.43 (0.16, 1.25)\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nOS rate at 3 years (%)\n<\/p>\n<\/td>\n

\n

\n30.0\n<\/p>\n<\/td>\n

\n

\n0.0\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nKRAS <\/i>mutation<\/b>\n<\/p>\n<\/td>\n

\n

\nn=60\n<\/p>\n<\/td>\n

\n

\nn=53\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nMedian OS (in months)\n<\/p>\n<\/td>\n

\n

\n25.7\n<\/p>\n<\/td>\n

\n

\n10.4\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nHazard ratio (95% CI)iv<\/sup>\n<\/p>\n<\/td>\n

\n

\n0.55 (0.36, 0.85)\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nOS rate at 3 years (%)\n<\/p>\n<\/td>\n

\n

\n40.0\n<\/p>\n<\/td>\n

\n

\n15.8\n<\/p>\n<\/td>\n<\/tr>\n<\/table>\n\n\n\n\n\n
\n

\ni.\n<\/p>\n<\/td>\n

\n

\nSTK11 and KRAS subgroup analyses were presented for patients with non-squamous histology; while the KEAP1 subgroup analysis was presented for all mutation-evaluable patients irrespective of tumor histology, due to a small sample size.\n<\/p>\n<\/td>\n<\/tr>\n

\n

\nii.\n<\/p>\n<\/td>\n

\n

\nData cut-off (DCO) date: 11 March 2022. Median follow-up in censored patients at DCO: 46.5 months (range 0.0\u201356.5)\n<\/p>\n<\/td>\n<\/tr>\n

\n

\niii.\n<\/p>\n<\/td>\n

\n

\nStratified analysis by PD-L1 expression (TC \u226550% vs <50%), disease stage (IVA vs IVB) and histology\n<\/p>\n<\/td>\n<\/tr>\n

\n

\niv.\n<\/p>\n<\/td>\n

\n

\nUnstratified analysis\u00a0\n<\/p>\n<\/td>\n<\/tr>\n<\/table>\n

\nTremelimumab plus IMFINZI and chemotherapy continued to be well-tolerated, with no new safety signals identified based on the collection of serious adverse events (AEs) during the approximately four-years of follow-up. Serious treatment-related AEs of any grade occurred in 27.6% of patients in the IMFINZI, tremelimumab and chemotherapy arm versus 17.7% in the chemotherapy alone arm as assessed by investigators. Treatment-related AEs leading to death occurred in 3.3% of patients in the combination arm versus 2.4% in the chemotherapy arm.\n<\/p>\n

\nThese updated results build on the primary progression-free survival (PFS) and OS results presented<\/a> at the 2021 World Conference on Lung Cancer (WCLC) in September 2021 as well as post-hoc exploratory results in patients with STK11, KEAP1 or KRAS-mutated metastatic NSCLC recently presented<\/a> at WCLC 2022 in August.\n<\/p>\n

\nTremelimumab is under review by global regulatory authorities in combination with IMFINZI and chemotherapy in 1st-line metastatic NSCLC based on the results of the POSEIDON trial.\n<\/p>\n

\nIMPORTANT SAFETY INFORMATION<\/b>\n<\/p>\n

\nThere are no contraindications for IMFINZI\u00ae<\/sup> (durvalumab).\n<\/p>\n

\nImmune-Mediated Adverse Reactions<\/b>\n<\/p>\n

\nImportant immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg\/kg\/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.\n<\/p>\n

\nImmune-Mediated Pneumonitis<\/b>\n<\/p>\n

\nIMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34\/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87\/475) in patients receiving IMFINZI and 12.8% (30\/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC when in combination with chemotherapy.\n<\/p>\n

\nImmune-Mediated Colitis<\/b>\n<\/p>\n

\nIMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection\/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37\/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.\n<\/p>\n

\nImmune-Mediated Hepatitis<\/b>\n<\/p>\n

\nIMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52\/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.\n<\/p>\n

\nImmune-Mediated Endocrinopathies<\/b>\n<\/p>\n